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Birgit Schittek - One of the best experts on this subject based on the ideXlab platform.
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the secrets of Dermcidin action
International Journal of Medical Microbiology, 2015Co-Authors: Marc Burian, Birgit SchittekAbstract:Antimicrobial peptides (AMPs) are important effector molecules of the innate immune defense of diverse species. The majority of known AMPs are cationic therefore facilitating the initial binding of the positively charged peptides to the negatively charged bacterial membrane. Dermcidin (DCD) is constitutively expressed in eccrine sweat glands, secreted into sweat and transported to the epidermal surface where it is proteolytically processed giving rise to several truncated DCD peptides. Its processed forms such as the anionic 48mer DCD-1L and the 47mer DCD-1 possess antimicrobial activity against numerous bacteria including Staphylococcus aureus. Here, the latest knowledge regarding the mode of action of the anionic DCD-1(L) and the functional consequences of their interaction with bacterial membranes is reviewed. There is evidence that the interaction of DCD-1(L) with negatively charged bacterial phospholipids leads to Zn2+ dependent formation of oligomeric complexes in the bacterial membrane, which subsequently leads to ion channel formation resulting in membrane depolarization and bacterial cell death.
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the multiple facets of Dermcidin in cell survival and host defense
Journal of Innate Immunity, 2012Co-Authors: Birgit SchittekAbstract:Eccrine sweat glands, which are distributed over the whole bodies of primates and humans, have long been regarded mainly to have a function in thermoregulation. However, the discovery of Dermcidin-derived antimicrobial peptides in eccrine sweat demonstrated that sweat actively participates in the constitutive innate immune defense of human skin against infection. In the meantime, a number of studies proved the importance of Dermcidin in skin host defense. Several reports also state that peptides processed from the Dermcidin precursor protein exhibit a range of other biological functions in neuronal and cancer cells. This review summarizes the evidence gathered until now concerning the expression of Dermcidin and the functional relevance of Dermcidin-derived peptides.
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staphylococcus aureus mutant screen reveals interaction of the human antimicrobial peptide Dermcidin with membrane phospholipids
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Kevin Rigby, Birgit Schittek, Yuping Lai, Vinod Nair, Andreas Peschel, Michael OttoAbstract:Antimicrobial peptides (AMPs) form an important part of the innate host defense. In contrast to most AMPs, human Dermcidin has an anionic net charge. To investigate whether bacteria have developed specific mechanisms of resistance to Dermcidin, we screened for mutants of the leading human pathogen, Staphylococcus aureus, with altered resistance to Dermcidin. To that end, we constructed a plasmid for use in mariner-based transposon mutagenesis and developed a high-throughput cell viability screening method based on luminescence. In a large screen, we did not find mutants with strongly increased susceptibility to Dermcidin, indicating that S. aureus has no specific mechanism of resistance to this AMP. Furthermore, we detected a mutation in a gene of unknown function that resulted in significantly increased resistance to Dermcidin. The mutant strain had an altered membrane phospholipid pattern and showed decreased binding of Dermcidin to the bacterial surface, indicating that Dermcidin interacts with membrane phospholipids. The mode of this interaction was direct, as shown by assays of Dermcidin binding to phospholipid preparations, and specific, as the resistance to other AMPs was not affected. Our findings indicate that Dermcidin has an exceptional value for the human innate host defense and lend support to the idea that it evolved to evade bacterial resistance mechanisms targeted at the cationic character of most AMPs. Moreover, they suggest that the antimicrobial activity of Dermcidin is dependent on the interaction with the bacterial membrane and might thus assist with the determination of the yet unknown mode of action of this important human AMP.
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resistance to Dermcidin derived peptides is independent of bacterial protease activity
International Journal of Antimicrobial Agents, 2009Co-Authors: Ilknur Senyurek, Hubert Kalbacher, Andreas Peschel, Martin Deeg, Gerd Doring, Christiane Wolz, Birgit SchittekAbstract:Dermcidin (DCD) is an antimicrobial peptide constitutively expressed in eccrine sweat glands in human skin. By post-secretory proteolytic processing in sweat, the DCD protein gives rise to anionic and cationic DCD peptides that are able to kill several Gram-positive and Gram-negative bacteria but are only weakly active against Pseudomonas aeruginosa. Here, we questioned whether bacterial resistance to DCD peptides is mediated by proteolytic degradation. It was shown that DCD-derived peptides are degraded by purified bacterial proteases and by extracellular proteases secreted by P. aeruginosa in a concentration-dependent manner. However, protease-deficient mutants of P. aeruginosa PAO1 lacking either lasA, lasB (elastase) or both showed a similar sensitivity towards DCD-derived peptides as the wild-type strain. Finally, inhibition of total protease activity indicated that proteases secreted by P. aeruginosa are not responsible for the poor activity of DCD-derived peptides against P. aeruginosa. These data suggest that the decreased sensitivity of P. aeruginosa to DCD-derived peptides is not mediated by proteolytic degradation under physiological conditions.
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naturally processed Dermcidin derived peptides do not permeabilize bacterial membranes and kill microorganisms irrespective of their charge
Antimicrobial Agents and Chemotherapy, 2006Co-Authors: Heiko Steffen, Hubert Kalbacher, Andreas Peschel, Claus Garbe, S Rieg, Imke Wiedemann, Martin Deeg, Hansgeorg Sahl, Friedrich Gotz, Birgit SchittekAbstract:Dermcidin (DCD) is a recently described antimicrobial peptide, which is constitutively expressed in eccrine sweat glands and transported via sweat to the epidermal surface. By postsecretory proteolytic processing in sweat the Dermcidin protein gives rise to several truncated DCD peptides which differ in length and net charge. In order to understand the mechanism of antimicrobial activity, we analyzed the spectrum of activity of several naturally processed Dermcidin-derived peptides, the secondary structure in different solvents, and the ability of these peptides to interact with or permeabilize the bacterial membrane. Interestingly, although all naturally processed DCD peptides can adopt an alpha-helical conformation in solvents, they have a diverse and partially overlapping spectrum of activity against gram-positive and gram-negative bacteria. This indicates that the net charge and the secondary structure of the peptides are not important for the toxic activity. Furthermore, using carboxyfluorescein-loaded liposomes, membrane permeability studies and electron microscopy we investigated whether DCD peptides are able to permeabilize bacterial membranes. The data convincingly show that irrespective of charge the different DCD peptides are not able to permeabilize bacterial membranes. However, bacterial mutants lacking specific cell envelope modifications exhibited different susceptibilities to killing by DCD peptides than wild-type bacterial strains. Finally, immunoelectron microscopy studies indicated that DCD peptides are able to bind to the bacterial surface; however, signs of membrane perturbation were not observed. These studies indicate that DCD peptides do not exert their activity by permeabilizing bacterial membranes.
Asru K Sinha - One of the best experts on this subject based on the ideXlab platform.
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estriol inhibits tnf aâ and il 6 production and promotes antiinflammatoryresponses via nitric oxide stimulation in Dermcidin isoform 2 stimulated neutrophil
Journal of Cell Science and Apoptosis, 2017Co-Authors: Pradipta Jana, Asru K Sinha, Santanu Guha, Gausal A Khan, Mobidullah Khan, Smarajit MaitiAbstract:Increase in the level of cytokines like TNF-α and IL-6 causes the inflammatory surge in acute ischemic heart disease (AIHD). Occurrence of a high level Dermcidin isoform-2 in AIHD demonstrates a possible regulation on cytokines expression. It was found that incubation of 120 nM of Dermcidin isoform-2 (DCN-2) to the normal neutrophil solution for 2 h resulted in the increase of synthesis of TNF-α from 3.829 ± 1.53 pg/ml to 20.7 ± 6.9 pg/ml and IL-6 from 3.27 ± 1.52 pg/ml to 47.07 ± 3.4 pg/ml. Cytokines were determined in AIHD patient blood with TNF-α level 18.3-27.3 pg/ml, median value 21.863 pg/ml and IL-6 23.54-52.733 pg/ml, median value 42.163 pg/ml. Treatment with 0.6 nM estriol, a kind of female steroid hormone estrogen for 45 min decreased the elevated cytokine level in 120 nM DCN-2 treated normal neutrophils. The expression of DCN-2 induced TNF-α synthesis in neutrophils was further determined by Western blot technique with a thickened band intensity of TNF-α in DCN-2 induced neutrophil solution. The production of nitric oxide (NO) was also regulated with the effect of DCN-2 treatment from 1.61 nmol NO/ml to 0 nmol NO/ml. The subsequent reduction of TNF-α level due to 0.6 nM estriol treatment had shown the corresponding increase in NO level to 0.559 nmol/ml. It can be concluded that production of DCN-2 due to stress in AIHD after heart attack propagate the inflammatory response. Steroid molecule like estriol plays a protective role by reducing DCN-2 responses through the NO synthesis.
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Dermcidin isoform 2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction
Scientific Reports, 2015Co-Authors: Sarbashri Bank, Pradipta Jana, Smarajit Maiti, Santanu Guha, Asru K SinhaAbstract:The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (Dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with Dermcidin showed one high affinity (Kd = 40 nM) and one low affinity binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4 μM Dermcidin, the platelets became resistant to the inhibitory effect of aspirin similar to that in the case of AMI. Incubation of PRP from AMI with Dermcidin antibody restored the sensitivity of the platelets to the aspirin effect. Incubation of AMI PRP pretreated with 15 μM aspirin, a stimulator of the NO synthesis, resulted in the increased production of NO in the platelets that removed the bound Dermcidin by 40% from the high affinity binding sites of AMI platelets. When the same AMI PRP was retreated with 10 μM aspirin, the aggregation of platelets was completely inhibited by NO synthesis.
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reduction by aspirin of death rate due to acute coronary syndrome in breast cancer by the normalization of Dermcidin isoform 2 a randomized parallel group trial
2015Co-Authors: D Banerjee, Rabindra Bhattacharya, Gannareddy V Girish, Sana Naz, Asru K SinhaAbstract:Background: As environmentally induced stresses has been reported to promote breast cancer in females, the association of Dermcidin isoform 2 (DCN-2), an environmentally induced major atherosclerotic risk factor in female breast cancer (fBC) subjects was investigated. Since the treatment of leukocytes with 15 µM aspirin inhibited DCN-2 synthesis, the effect of oral administration of 14 mg aspirin/70 kg body weight to fBC subjects was performed to find out the reduction if any, of death rate due to acute coronary syndrome (ACS). Methods: Synthesis of DCN-2 in leukocytes was determined by in-vitro translation of mRNA and quantitated by Enzyme Linked Immunosorbent Assay. Nitric oxide was determined by methemoglobin method. fBC (n = 1140) were asked to ingest of aspirin everyday for 2years and the plasma Dermcidin level was determined. The death rate due to ACS was determined by Z-test. Results: DCN-2 in fBC patients was found to be increased to 36.75 ± 0.85 nM from 15.50 ± 0.64 nM (p<0.0001). After oral ingestion of 14 mg/70 kg body weight aspirin (n=1140), the death rate due to ACS in fBC decreased to 10.43% from ≈50% as determined by Z-test (Z-score=5.89, p<0.0001). Conclusion: The increased incidence of ACS in fBC could be related to the increase of plasma DCN-2 level, a major risk factor for atherosclerosis and oral administration of aspirin could be helpful to reduce the death rate due to ACS in breast cancer by reducing systemic DCN-2 synthesis.
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the effect of acetyl salicylic acid induced nitric oxide synthesis in the normalization of hypertension through the stimulation of renal cortexin synthesis and by the inhibition of Dermcidin isoform 2 a hypertensive protein production
International journal of biomedical science : IJBS, 2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Santanu Guha, Uttam K Maji, Asru K SinhaAbstract:Currently, there is no specific medication for essential hypertension (EH), a major form of the condition, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit Dermcidin isoform 2 (Dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of Dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man.
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the diagnosis of high altitude illness by the determination of plasma Dermcidin isoform 2 levels by enzyme linked immunosorbent assay
Clinical Laboratory, 2014Co-Authors: Sarbashri Bank, Rajeshwary Ghosh, Pradipta Jana, Suman Bhattacharya, Asru K SinhaAbstract:BACKGROUND High altitude illness (HAI) is a cluster of syndromes which develops due to the injury of the central nervous system produced by the reduction of the partial pressure of O2 in the atmosphere which disappears on decent. The HAI also results in a prothrombotic condition leading to acute coronary syndrome (ACS), which cannot be controlled on descent to the ground level. There is no diagnosis in HAI to forewarn of the impending ACS. A protein identified to be Dermcidin isoform 2 (Dermcidin), produced in the system due to environmental stresses, has been reported to be a potent diabetogenic agent. Investigation was carried out to determine the systemic stimulation of Dermcidin synthesis at different levels of altitudes in normal adult male volunteers to assess the feasibility of developing a diagnosis for ACS in HAI due to Dermcidin synthesis. METHODS Normal, nondiabetic, normotensive male volunteers (25 - 35 years old, n = 16) participated in the study. The plasma Dermcidin level was determined by enzyme linked immunosorbent assay (ELISA) and by in vitro translation of Dermcidin mRNA. The plasma insulin level was determined by ELISA and blood glucose level was determined in a glucometer (Behringer). RESULTS The plasma Dermcidin level in the volunteers at ground level was 10 +/- 2.10 nM and increased to 80 +/- 4.62 nM at 15000 feet altitude. For each 1000 feet increase of altitude, the Dermcidin level increased by 5.83 +/- 0.21 nM with a Coefficient of Correlation "r" = +0.9405. The increase of plasma Dermcidin level was found to be inversely related to the decrease of plasma insulin level from 23 microunit/mL to 5 microunit/mL from sea level to 15000 feet height ("r" = -0.9951) with concomitant increase of blood sugar level from 80 +/- 3.6 mg/dL to 135 +/- 2.01 mg/dL. CONCLUSIONS These results suggest the feasibility of a diagnosis of a prediabetic condition by determining the plasma Dermcidin level in HAI by simple ELISA which may also be useful to forewarn of the possibility of developing an impending prothrombotic condition in HAI.
Sarbashri Bank - One of the best experts on this subject based on the ideXlab platform.
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stress induced protein Dermcidin develops diabetes targeting glut4 insulinviano cgmp inhibition
British Journal of Pharmacology, 2021Co-Authors: Sarbashri Bank, Suman Bhattacharya, Smarajit Maiti, Andreas Koschinski, Manuela Zaccolo, Amrita Banerjee, Gausal A Khan, Madhusudan Das, Santanu GuhaAbstract:BACKGROUND AND PURPOSE Diabetes is common in tobacco-consuming individuals, hypoxia-encountering people, and post-menopausal women. The mechanism behind diabetes-associated vascular-dysfunction remains speculative. Dermcidin (DCD), an 11 kDa-protein plays a detrimental role in acute myocardial-infarction through the impairment of endothelial-nitric-oxide-synthase (eNOS). EXPERIMENTAL APPROACH DCD mediated genesis of diabetes has been manifested in human and rodent-models under various stress-conditions. Here, plasma levels of DCD have been significantly correlated with the diabetic-conditions in postmenopausal-women, in tobacco-consuming individuals and in hypoxia indicating a common pathway. In mice, DCD infusion augmented the blood glucose with a concomitant reduction of nitric oxide levels. DCD triggers the release of glucose from the liver/muscle/kidney and antagonizes the effects of insulin. This has been demonstrated by the glucose tolerance and insulin tolerance test. Herein our studies showed that DCD inhibited GLUT-4 and impaired NO production. KEY RESULTS We showed that tobacco consumption or hypoxia might provoke DCD-induced hyperglycemia by down-regulation of NO-signaling, GLUT4-function, and insulin sensitivity. Tobacco-induced DCD up-regulation has been shown in RT-PCR and qPCR results and DCD-induced lower insulin-sensitivity has been shown by Western-blot. The insulin, GLUT-4, and GANOS expression were missing in postmenopausal women due to DCD. Our FRET-imaging studies demonstrate that DCD-induced NO deregulation impairs cGMP-mediated cellular-signaling. CONCLUSIONS & IMPLICATIONS Molecular-docking experiments (AUTODOCK/PATCHDOCK) decisively showed high-affinity binding of DCD to GLUT-4, insulin, and its receptor (Ectodomain1/2). Synergism of all these effects resulted in the breakdown of glucose homeostasis-machinery i.e. insulin-resistance, and further Dermcidin induced NO/cGMP down-regulation in individuals under a variety of stressors.
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stress induced protein Dermcidin develops diabetes targeting glut4 insulin via no cgmp inhibition
Social Science Research Network, 2019Co-Authors: Sarbashri Bank, Suman Bhattacharya, Smarajit Maiti, Santanu Guha, Andreas Koschinski, Manuela Zaccolo, Amrita Banerjee, Gausal A Khan, Arjun K Ghosh, Udayan RayAbstract:Diabetes is highly prevalent in tobacco-consuming individuals, hypoxia-experiencing persons and post-menopausal women. The mechanism behind diabetes-associated vascular-disorders remains speculative. Dermcidin, an 11 kDa-protein plays a crucial role in acute myocardial infarction through the inhibition of nitric-oxide synthase. Therefore, Dermcidin has been tested in the genesis of diabetes in human and rodentmodels under different physiological conditions. In these investigations blood levels of dermdicin significantly correlated with the diabetic condition in post-menopausal women, in tobacco consuming individuals and in hypoxic person indicating a common pathway. In mice, injection of Dermcidin augmented the blood sugar level with a concomitant reduction of nitric-oxide levels. Dermcidin triggers the release of glucose from liver/muscle/kidney; and antagonizes the effects of insulin even more effectively than glucagon. Immunohistochemical studies showed that Dermcidin inhibits GLUT-4 translocation and impairs nitric-oxide production. Here, we show that tobacco consumption or hypoxia might provoke hyperglycemia induced by Dermcidin by concomitant down regulation of NO-signaling, GLUT4-function and insulin-sensitivity. Largest representative of haematopoetic cell, neutrophils show significantly increased glucose mediated insulin, GLUT-4 and GANOS expression which was missing in postmenopausal women due to the Dermcidin effect. Bioinformatics study with protein networking (STRING) analysis suggests DCN role on soluble guanylate-cylase activity in higher primate. Our FRET-imaging studies demonstrate that DCD-induced NO deregulation impairs cGMP mediated cellular signaling. Molecular docking experiments (AUTODOC/PATCHDOC) decisively show high affinity binding of DCN to GLUT-4, insulin and its receptor (Ectodomain 1/2). Synergisms of these effects result in breakdown of glucose homeostasis machinery in individuals under wide variety of stressors. Funding Statement: The authors state: "No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interests: The authors declare: "None." Ethics Approval Statement: The protocols for both animal and human sample experiments were approved by the Institutional Review Board, Human & Animal Research Ethics Committee, Sinha Institute of Medical Science and Technology, Kolkata, India. The protocol strictly followed the Human ethics according to the 1964 Helsinki Declaration and National Institutes of Health, USA guidelines.
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the role of Dermcidin isoform 2 in the occurrence and severity of diabetes
Scientific Reports, 2017Co-Authors: Suman Bhattacharya, Sarbashri Bank, Md Mobidullah Khan, Chandradipa Ghosh, Smarajit MaitiAbstract:Diabetes is now epidemic worldwide. Several hundred-million peoples are presently suffering from this disease with other secondary-disorders. Stress, hypertension, sedentary life-style, carbohydrate/lipid metabolic-disorders due to genetic or environmental factors attributes to type-1 and/or type-2 diabetes. Present investigation demonstrates that stress-induced protein Dermcidin isoform-2 (DCN-2) which appears in the serum of diabetic-patients play a key-role in this disease pathogenesis/severity. DCN-2 suppresses insulin production-release from liver/pancreas. It also increases the insulin-resistance. Stress-induction at the onset/progression of this disease is noticed as the high-level of lipid peroxides/low-level of free-thiols in association with increase of inflammatory-markers c-reactive protein and TNF-α. DCN-2 induced decrease in the synthesis of glucose-activated nitric oxide synthase (GANOS) and lower production of NO in liver has been shown here where NO is demonstrated to lower the expression of glucose trabsporter-4 (GLUT-4) and its translocation on liver membrane surface. This finally impairs glucose transport to organs from the extracellular fluid. Low level of glucose uptake further decreases glucose-induced insulin synthesis. The central role of DCN-2 has been demonstrated in type-1/type-2 diabetic individuals, in rodent hepatocytes and pancreatic-cell, tissue-slices, in-vitro and in-vivo experimental model. It can be concluded that stress-induced decrease in insulin synthesis/function, glucose transport is an interactive consequence of oxidative threats and inflammatory events.
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Dermcidin isoform 2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction
Scientific Reports, 2015Co-Authors: Sarbashri Bank, Pradipta Jana, Smarajit Maiti, Santanu Guha, Asru K SinhaAbstract:The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (Dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with Dermcidin showed one high affinity (Kd = 40 nM) and one low affinity binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4 μM Dermcidin, the platelets became resistant to the inhibitory effect of aspirin similar to that in the case of AMI. Incubation of PRP from AMI with Dermcidin antibody restored the sensitivity of the platelets to the aspirin effect. Incubation of AMI PRP pretreated with 15 μM aspirin, a stimulator of the NO synthesis, resulted in the increased production of NO in the platelets that removed the bound Dermcidin by 40% from the high affinity binding sites of AMI platelets. When the same AMI PRP was retreated with 10 μM aspirin, the aggregation of platelets was completely inhibited by NO synthesis.
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the effect of acetyl salicylic acid induced nitric oxide synthesis in the normalization of hypertension through the stimulation of renal cortexin synthesis and by the inhibition of Dermcidin isoform 2 a hypertensive protein production
International journal of biomedical science : IJBS, 2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Santanu Guha, Uttam K Maji, Asru K SinhaAbstract:Currently, there is no specific medication for essential hypertension (EH), a major form of the condition, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit Dermcidin isoform 2 (Dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of Dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man.
Rajeshwary Ghosh - One of the best experts on this subject based on the ideXlab platform.
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the effect of acetyl salicylic acid induced nitric oxide synthesis in the normalization of hypertension through the stimulation of renal cortexin synthesis and by the inhibition of Dermcidin isoform 2 a hypertensive protein production
International journal of biomedical science : IJBS, 2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Santanu Guha, Uttam K Maji, Asru K SinhaAbstract:Currently, there is no specific medication for essential hypertension (EH), a major form of the condition, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit Dermcidin isoform 2 (Dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of Dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man.
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neutralization by insulin of the hypertensive effect of Dermcidin isoform 2 an environmentally induced diabetogenic and hypertensive protein
Cardiology Research and Practice, 2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Kumar A SinhaAbstract:The effect of Dermcidin isoform 2 (Dermcidin), an environmentally induced stress protein, was investigated on the genesis of diabetes mellitus and hypertension, the two major atherosclerotic risk factors. The role of Dermcidin as an atherosclerotic risk factor related to the impaired systemic insulin level was investigated. Dermcidin was prepared by electrophoresis using plasma from the subjects with acute ischemic heart disease. Injection of 0.2 M Dermcidin in mice increased the blood glucose level from mg/dL to mg/dL which was normalized by the oral administration of acetyl salicylic acid (aspirin) after 24 h. Hypertensive subjects with systolic and diastolic blood pressure of 165 mm and 95 mm of Hg, respectively, had plasma Dermcidin level of 95 nM. Ingestion of acetyl salicylic acid (aspirin) (150 mg/70 kg body weight) decreased the systolic and diastolic pressures to 125 mm and 80 mm of Hg, respectively, with decrease of Dermcidin level to 15 nM. Incubation of kidney cortex cells with 0.2 M Dermcidin-inhibited synthesis of (r)-cortexin, an antihypertensive protein, and the basal (r)-cortexin level was reduced from 33 nM to 15 nM. Addition of 25 units of insulin/mL was found to reverse the inhibition of cortexin synthesis. The effect of Dermcidin as a diabetogenic and a hypertensive agent could be controlled either by aspirin or by insulin.
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the diagnosis of high altitude illness by the determination of plasma Dermcidin isoform 2 levels by enzyme linked immunosorbent assay
Clinical Laboratory, 2014Co-Authors: Sarbashri Bank, Rajeshwary Ghosh, Pradipta Jana, Suman Bhattacharya, Asru K SinhaAbstract:BACKGROUND High altitude illness (HAI) is a cluster of syndromes which develops due to the injury of the central nervous system produced by the reduction of the partial pressure of O2 in the atmosphere which disappears on decent. The HAI also results in a prothrombotic condition leading to acute coronary syndrome (ACS), which cannot be controlled on descent to the ground level. There is no diagnosis in HAI to forewarn of the impending ACS. A protein identified to be Dermcidin isoform 2 (Dermcidin), produced in the system due to environmental stresses, has been reported to be a potent diabetogenic agent. Investigation was carried out to determine the systemic stimulation of Dermcidin synthesis at different levels of altitudes in normal adult male volunteers to assess the feasibility of developing a diagnosis for ACS in HAI due to Dermcidin synthesis. METHODS Normal, nondiabetic, normotensive male volunteers (25 - 35 years old, n = 16) participated in the study. The plasma Dermcidin level was determined by enzyme linked immunosorbent assay (ELISA) and by in vitro translation of Dermcidin mRNA. The plasma insulin level was determined by ELISA and blood glucose level was determined in a glucometer (Behringer). RESULTS The plasma Dermcidin level in the volunteers at ground level was 10 +/- 2.10 nM and increased to 80 +/- 4.62 nM at 15000 feet altitude. For each 1000 feet increase of altitude, the Dermcidin level increased by 5.83 +/- 0.21 nM with a Coefficient of Correlation "r" = +0.9405. The increase of plasma Dermcidin level was found to be inversely related to the decrease of plasma insulin level from 23 microunit/mL to 5 microunit/mL from sea level to 15000 feet height ("r" = -0.9951) with concomitant increase of blood sugar level from 80 +/- 3.6 mg/dL to 135 +/- 2.01 mg/dL. CONCLUSIONS These results suggest the feasibility of a diagnosis of a prediabetic condition by determining the plasma Dermcidin level in HAI by simple ELISA which may also be useful to forewarn of the possibility of developing an impending prothrombotic condition in HAI.
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The Effect of Acetyl Salicylic Acid Induced Nitric Oxide Synthesis in the Normalization of Hypertension through the Stimulation of Renal Cortexin Synthesis and by the Inhibition of Dermcidin Isoform 2, A Hypertensive Protein Production
2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Santanu Guha, Uttam K Maji, Kumar A SinhaAbstract:AbstrAct Currently, there is no specific medication for essential hypertension (EH), a major form of the condi-tion, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit Dermcidin isoform 2 (Dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of Dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man. (Int J Biomed Sci 2014; 10 (3): 158-166
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the role of Dermcidin isoform 2 a two faceted atherosclerotic risk factor for coronary artery disease and the effect of acetyl salicylic acid on it
Thrombosis, 2012Co-Authors: Rajeshwary Ghosh, Rabindra Bhattacharya, Uttam K Maji, Asru K SinhaAbstract:Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be Dermcidin isoform 2 of Mr. 11 kDa from blood plasma of hypertensive persons when injected (0.1 μM) in rabbits increased the systolic pressure by 77% and diastolic pressure by 45% over the controls within 2 h. Ingestion of acetyl salicylic acid (150 mg/70 kg) by these subjects reduced systolic (130 mm Hg) and diastolic pressures (80 mm Hg) with reduction of plasma Dermcidin level to normal ranges (9 nM). The protein was found to be a potent activator of platelet cyclooxygenase and inhibited insulin synthesis. Aspirin was found to reduce hypertension by reduction of plasma Dermcidin level, neutralized the effect of cyclooxygenase, and restored the pancreatic insulin synthesis through NO synthesis. These results indicated that Dermcidin could be a novel atherosclerotic risk factor for its hypertensive and diabetogenic effects.
Rabindra Bhattacharya - One of the best experts on this subject based on the ideXlab platform.
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reduction by aspirin of death rate due to acute coronary syndrome in breast cancer by the normalization of Dermcidin isoform 2 a randomized parallel group trial
2015Co-Authors: D Banerjee, Rabindra Bhattacharya, Gannareddy V Girish, Sana Naz, Asru K SinhaAbstract:Background: As environmentally induced stresses has been reported to promote breast cancer in females, the association of Dermcidin isoform 2 (DCN-2), an environmentally induced major atherosclerotic risk factor in female breast cancer (fBC) subjects was investigated. Since the treatment of leukocytes with 15 µM aspirin inhibited DCN-2 synthesis, the effect of oral administration of 14 mg aspirin/70 kg body weight to fBC subjects was performed to find out the reduction if any, of death rate due to acute coronary syndrome (ACS). Methods: Synthesis of DCN-2 in leukocytes was determined by in-vitro translation of mRNA and quantitated by Enzyme Linked Immunosorbent Assay. Nitric oxide was determined by methemoglobin method. fBC (n = 1140) were asked to ingest of aspirin everyday for 2years and the plasma Dermcidin level was determined. The death rate due to ACS was determined by Z-test. Results: DCN-2 in fBC patients was found to be increased to 36.75 ± 0.85 nM from 15.50 ± 0.64 nM (p<0.0001). After oral ingestion of 14 mg/70 kg body weight aspirin (n=1140), the death rate due to ACS in fBC decreased to 10.43% from ≈50% as determined by Z-test (Z-score=5.89, p<0.0001). Conclusion: The increased incidence of ACS in fBC could be related to the increase of plasma DCN-2 level, a major risk factor for atherosclerosis and oral administration of aspirin could be helpful to reduce the death rate due to ACS in breast cancer by reducing systemic DCN-2 synthesis.
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the effect of acetyl salicylic acid induced nitric oxide synthesis in the normalization of hypertension through the stimulation of renal cortexin synthesis and by the inhibition of Dermcidin isoform 2 a hypertensive protein production
International journal of biomedical science : IJBS, 2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Santanu Guha, Uttam K Maji, Asru K SinhaAbstract:Currently, there is no specific medication for essential hypertension (EH), a major form of the condition, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit Dermcidin isoform 2 (Dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of Dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man.
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neutralization by insulin of the hypertensive effect of Dermcidin isoform 2 an environmentally induced diabetogenic and hypertensive protein
Cardiology Research and Practice, 2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Kumar A SinhaAbstract:The effect of Dermcidin isoform 2 (Dermcidin), an environmentally induced stress protein, was investigated on the genesis of diabetes mellitus and hypertension, the two major atherosclerotic risk factors. The role of Dermcidin as an atherosclerotic risk factor related to the impaired systemic insulin level was investigated. Dermcidin was prepared by electrophoresis using plasma from the subjects with acute ischemic heart disease. Injection of 0.2 M Dermcidin in mice increased the blood glucose level from mg/dL to mg/dL which was normalized by the oral administration of acetyl salicylic acid (aspirin) after 24 h. Hypertensive subjects with systolic and diastolic blood pressure of 165 mm and 95 mm of Hg, respectively, had plasma Dermcidin level of 95 nM. Ingestion of acetyl salicylic acid (aspirin) (150 mg/70 kg body weight) decreased the systolic and diastolic pressures to 125 mm and 80 mm of Hg, respectively, with decrease of Dermcidin level to 15 nM. Incubation of kidney cortex cells with 0.2 M Dermcidin-inhibited synthesis of (r)-cortexin, an antihypertensive protein, and the basal (r)-cortexin level was reduced from 33 nM to 15 nM. Addition of 25 units of insulin/mL was found to reverse the inhibition of cortexin synthesis. The effect of Dermcidin as a diabetogenic and a hypertensive agent could be controlled either by aspirin or by insulin.
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The Effect of Acetyl Salicylic Acid Induced Nitric Oxide Synthesis in the Normalization of Hypertension through the Stimulation of Renal Cortexin Synthesis and by the Inhibition of Dermcidin Isoform 2, A Hypertensive Protein Production
2014Co-Authors: Rajeshwary Ghosh, Sarbashri Bank, Rabindra Bhattacharya, Nighat N Khan, Santanu Guha, Uttam K Maji, Kumar A SinhaAbstract:AbstrAct Currently, there is no specific medication for essential hypertension (EH), a major form of the condi-tion, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit Dermcidin isoform 2 (Dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of Dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man. (Int J Biomed Sci 2014; 10 (3): 158-166
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the role of Dermcidin isoform 2 a two faceted atherosclerotic risk factor for coronary artery disease and the effect of acetyl salicylic acid on it
Thrombosis, 2012Co-Authors: Rajeshwary Ghosh, Rabindra Bhattacharya, Uttam K Maji, Asru K SinhaAbstract:Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be Dermcidin isoform 2 of Mr. 11 kDa from blood plasma of hypertensive persons when injected (0.1 μM) in rabbits increased the systolic pressure by 77% and diastolic pressure by 45% over the controls within 2 h. Ingestion of acetyl salicylic acid (150 mg/70 kg) by these subjects reduced systolic (130 mm Hg) and diastolic pressures (80 mm Hg) with reduction of plasma Dermcidin level to normal ranges (9 nM). The protein was found to be a potent activator of platelet cyclooxygenase and inhibited insulin synthesis. Aspirin was found to reduce hypertension by reduction of plasma Dermcidin level, neutralized the effect of cyclooxygenase, and restored the pancreatic insulin synthesis through NO synthesis. These results indicated that Dermcidin could be a novel atherosclerotic risk factor for its hypertensive and diabetogenic effects.