The Experts below are selected from a list of 2403 Experts worldwide ranked by ideXlab platform

Nipasiri Voraphani - One of the best experts on this subject based on the ideXlab platform.

Xin L - One of the best experts on this subject based on the ideXlab platform.

  • tnfα initiated oxidative Nitrative Stress mediates cardiomyocyte apoptosis in traumatic animals
    Apoptosis, 2007
    Co-Authors: Shuzhuang Li, Bernard L Lopez, Theodore A Christopher, Xiangying Jiao, Rong Hua Luan, Xin L
    Abstract:

    Whole body non-penetrating trauma causes myocardial infarction in humans and mechanical trauma (MT) results in cardiac dysfunction in animals. Our recent study demonstrated that incubation of cardiomyocytes with plasma isolated from MT animals causes significant cardiomyocyte apoptosis that can be blocked by neutralization of TNFα. The present study attempted to obtain direct in vivo evidence to support that overproduction of TNFα plays a causative role in trauma-induced cardiomyocyte apoptosis. Non-lethal MT caused significant TNFα overproduction (2.4-fold at 1.5 h after MT) and increased cardiomyocyte apoptosis (starting 3 h and peaking 12 h after MT). Pharmacological inhibition of TNFα with etanercept or TNFα gene deletion reduced post-trauma myocyte apoptosis (P < 0.01). Expression of iNOS and NADPH oxidase, overproduction of NO and \( {\text{O}}^{ - }_{2} \), and excessive protein nitration in the MT heart were all significantly reduced in etanercept-treated or TNFα−/− mice, suggesting that oxidative/Nitrative Stress may contribute to TNFα-initiated myocyte apoptosis in MT hearts. Additional experiments demonstrated that inhibiting iNOS (1400W) or NADPH oxidase (apocynin), or scavenging peroxynitrite (FP15) significantly reduced myocyte apoptosis in MT animals (P < 0.01). Collectively, these data demonstrated that non-lethal mechanical trauma caused significant TNFα production that in turn stimulated myocardial apoptosis via oxidative/Nitrative Stress.

  • TNFα-initiated oxidative/Nitrative Stress mediates cardiomyocyte apoptosis in traumatic animals
    Apoptosis, 2007
    Co-Authors: Shuzhuang Li, Bernard L Lopez, Theodore A Christopher, Xiangying Jiao, Rong Hua Luan, Xin L
    Abstract:

    Whole body non-penetrating trauma causes myocardial infarction in humans and mechanical trauma (MT) results in cardiac dysfunction in animals. Our recent study demonstrated that incubation of cardiomyocytes with plasma isolated from MT animals causes significant cardiomyocyte apoptosis that can be blocked by neutralization of TNFα. The present study attempted to obtain direct in vivo evidence to support that overproduction of TNFα plays a causative role in trauma-induced cardiomyocyte apoptosis. Non-lethal MT caused significant TNFα overproduction (2.4-fold at 1.5 h after MT) and increased cardiomyocyte apoptosis (starting 3 h and peaking 12 h after MT). Pharmacological inhibition of TNFα with etanercept or TNFα gene deletion reduced post-trauma myocyte apoptosis (P < 0.01). Expression of iNOS and NADPH oxidase, overproduction of NO and \( {\text{O}}^{ - }_{2} \), and excessive protein nitration in the MT heart were all significantly reduced in etanercept-treated or TNFα−/− mice, suggesting that oxidative/Nitrative Stress may contribute to TNFα-initiated myocyte apoptosis in MT hearts. Additional experiments demonstrated that inhibiting iNOS (1400W) or NADPH oxidase (apocynin), or scavenging peroxynitrite (FP15) significantly reduced myocyte apoptosis in MT animals (P < 0.01). Collectively, these data demonstrated that non-lethal mechanical trauma caused significant TNFα production that in turn stimulated myocardial apoptosis via oxidative/Nitrative Stress.

  • thioredoxin reduces post ischemic myocardial apoptosis by reducing oxidative Nitrative Stress
    British Journal of Pharmacology, 2006
    Co-Authors: A. Hu, Bernard L Lopez, Theodore A Christopher, Xin L, Walter J Koch, C Coletti, Yang Wang
    Abstract:

    Background and purpose: Thioredoxin (Trx) is an oxidoreductase that prevents free radical-induced cell death in cultured cells. Here we assessed the mechanism(s) underlying the cardioprotective effects of Trx in vivo. Experimental approach: The effects of myocardial ischemia (30 min) and reperfusion were measured in mice, with assays of myocardial apoptosis, superoxide production, NOx and nitrotyrosine content, and myocardial infarct size. Recombinant human Trx (rhTrx, 0.7–20 mg kg-1, i.p.) was given 10 min before reperfusion. Key results: Treatment with 2 mg kg-1 rhTrx significantly decreased myocardial apoptosis and reduced infarct size (P<0.01). Nitrotyrosine content of cardiomyocytes was markedly reduced in rhTrx-treated animals (P<0.01). To further identify the mechanisms by which rhTrx may exert its anti-Nitrative effect, iNOS expression and production of NOx and superoxide were determined. Treatment with rhTrx had no significant effect on iNOS expression or NOx content in the ischemic/reperfused heart. However, it markedly upregulated mSOD and reduced tissue superoxide content. To further establish a causative link between the anti- peroxynitrite effect and the cardioprotective effect of rhTrx, cultured adult cardiomyocytes were incubated with SIN-1, a peroxynitrite donor, (50 μM for 3 h) resulting in a nitrotyrosine content comparable to that seen in the ischemic/reperfused heart and causing significant cardiomyocyte apoptosis (P<0.01). Treatment with rhTrx markedly decreased SIN-1 induced apoptosis (P<0.01). Conclusions and implications: These results demonstrate that Trx is a novel anti-apoptotic and cardioprotective molecule that exerts its cardioprotective effects by reducing ischemia/reperfusion-induced oxidative/Nitrative Stress. British Journal of Pharmacology (2006) 149, 311–318. doi:10.1038/sj.bjp.0706853

  • chronic β adrenergic receptor stimulation induces cardiac apoptosis and aggravates myocardial ischemia reperfusion injury by provoking inducible nitric oxide synthase mediated Nitrative Stress
    Journal of Pharmacology and Experimental Therapeutics, 2006
    Co-Authors: A. Hu, Xiangying Jiao, Walter J Koch, Said Sharifiazad, Zvi Grunwald, Xin L
    Abstract:

    The present study provides evidence that inducible nitric-oxide synthase (iNOS)-mediated Nitrative Stress plays a pivotal role in chronic β-adrenergic receptor (AR) stimulation-induced cardiac damage. In mice, 14 days of isoproterenol (ISO) stimulation via an osmotic minipump induced an up-regulation of iNOS as evidenced by increases in mRNA, protein expression, and immunochemical staining of myocardial iNOS. Serum level of C-reactive protein, an inflammatory mediator, was also markedly increased. Under chronic ISO stimulation, the up-regulated iNOS produced a significantly increased amount of nitric oxide (NO) and its byproduct, peroxynitrite, in the circulation and heart and subsequently resulted in an accelerated myocardial apoptosis. Forty-minute myocardial ischemia (MI) and 24-h reperfusion (R) further increased NO production and peroxynitrite formation and resulted in an enlarged infarct size in mice receiving chronic ISO stimulation. However, the treatment with a selective iNOS inhibitor [ N -(3-(aminomethyl) benzyl)acetamidine] (1400W) or the use of a genetic modified animal (iNOS-knockout mice) markedly reduced iNOS-mediated production of NO and formation of peroxynitrite and consequently significantly decreased myocardial apoptosis and infarct size, showing a crucial link between iNOS-mediated Nitrative Stress and myocardial injury. In conclusion, chronic β-AR stimulation up-regulates iNOS expression and increases NO production in the heart, which subsequently markedly enhances formation of reactive nitrogen species/peroxynitrite in the heart, thereby eliciting myocardial apoptosis and potentiating MI/R injury.

Fereidoon Shahidi - One of the best experts on this subject based on the ideXlab platform.

  • trans trans 2 4 decadienal impairs vascular endothelial function by inducing oxidative Nitrative Stress and apoptosis
    Redox biology, 2020
    Co-Authors: Yuanyuan Hu, Zhenlong Yu, Yulin Peng, Guanhua Zhao, Da-yong Zhou, Fereidoon Shahidi
    Abstract:

    Abstract Aldehydes are implicated in the development of hypertension. Trans, trans-2,4-decadienal (tt-DDE), a dietary α,β-unsaturated aldehyde, is widespread in many food products. However, the role of tt-DDE in the pathophysiology of hypertension remains unknown. This study was designed to investigate whether tt-DDE consumption evokes hypertension and to explore the mechanisms underlying such a role. Sprague-Dawley rats were administered different concentrations of tt-DDE. After 28 days, blood pressure and endothelial function of mesenteric arteries were measured. Results showed that tt-DDE treatment significantly increased blood pressure and impaired endothelial function based on endothelium-dependent vasorelaxation and p-VASP levels. Mechanistically, tt-DDE induced oxidative/Nitrative Stress in the arteries of rats as evidenced by overproductions of superoxide and peroxynitrite, accompanied with increased expressions of iNOS and gp91phox. To further investigate the effects of tt-DDE on endothelial cells and underlying mechanisms, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of tt-DDE. tt-DDE induced oxidative/Nitrative Stress in HUVECs. Moreover, tt-DDE induced endothelial cells apoptosis through JNK-mediated signaling pathway. These results show, for the first time, that oral intake of tt-DDE elevates blood pressure and induces endothelial dysfunction in rats through oxidative/Nitrative Stress and JNK-mediated apoptosis signaling, indicating that excess ingestion of tt-DDE is a potential risk factor for endothelial dysfunction and hypertension.

  • Trans, trans-2,4-decadienal impairs vascular endothelial function by inducing oxidative/Nitrative Stress and apoptosis.
    Redox biology, 2020
    Co-Authors: Yuanyuan Hu, Zhenlong Yu, Yulin Peng, Guanhua Zhao, Da-yong Zhou, Xiaochi Ma, Fereidoon Shahidi
    Abstract:

    Abstract Aldehydes are implicated in the development of hypertension. Trans, trans-2,4-decadienal (tt-DDE), a dietary α,β-unsaturated aldehyde, is widespread in many food products. However, the role of tt-DDE in the pathophysiology of hypertension remains unknown. This study was designed to investigate whether tt-DDE consumption evokes hypertension and to explore the mechanisms underlying such a role. Sprague-Dawley rats were administered different concentrations of tt-DDE. After 28 days, blood pressure and endothelial function of mesenteric arteries were measured. Results showed that tt-DDE treatment significantly increased blood pressure and impaired endothelial function based on endothelium-dependent vasorelaxation and p-VASP levels. Mechanistically, tt-DDE induced oxidative/Nitrative Stress in the arteries of rats as evidenced by overproductions of superoxide and peroxynitrite, accompanied with increased expressions of iNOS and gp91phox. To further investigate the effects of tt-DDE on endothelial cells and underlying mechanisms, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of tt-DDE. tt-DDE induced oxidative/Nitrative Stress in HUVECs. Moreover, tt-DDE induced endothelial cells apoptosis through JNK-mediated signaling pathway. These results show, for the first time, that oral intake of tt-DDE elevates blood pressure and induces endothelial dysfunction in rats through oxidative/Nitrative Stress and JNK-mediated apoptosis signaling, indicating that excess ingestion of tt-DDE is a potential risk factor for endothelial dysfunction and hypertension.

Serpil C Erzurum - One of the best experts on this subject based on the ideXlab platform.

Gergő Szűcs - One of the best experts on this subject based on the ideXlab platform.

  • mechanisms and modulation of oxidative Nitrative Stress in type 4 cardio renal syndrome and renal sarcopenia
    Frontiers in Physiology, 2018
    Co-Authors: Marta Sarkozy, Renata Gaspar, Z A Kovacs, Monika G Kovacs, Gergő Szűcs
    Abstract:

    Chronic kidney disease (CKD) is a public health problem and a recognized risk factor for cardiovascular disease (CVD). CKD could amplify the progression of chronic heart failure leading to the development of type 4 cardio-renal syndrome (T4CRS). The severity and persistence of heart failure are strongly associated with mortality risk in T4CRS. CKD is also a catabolic state leading to renal sarcopenia which is defined as the loss of skeletal muscle strength and physical function. Renal sarcopenia also promotes the development of CVD and increases the mortality in CKD patients. In turn, heart failure developed in T4CRS could result in chronic muscle hypoperfusion and metabolic disturbances leading to or aggravating the renal sarcopenia. The interplay of multiple factors (e.g., comorbidities, the over-activated renin-angiotensin-aldosterone system [RAAS], the sympathetic nervous system [SNS], oxidative/Nitrative Stress, inflammation, etc.) may result in the progression of T4CRS and renal sarcopenia. Among these factors, oxidative/Nitrative Stress plays a crucial role in the complex pathomechanism and interrelationship between T4CRS and renal sarcopenia. In the heart and skeletal muscle, mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, uncoupled nitric oxide synthase (NOS) and xanthine oxidase are major ROS sources producing superoxide anion (O2•−) and/or hydrogen peroxide (H2O2). O2•− reacts with nitric oxide (NO) forming peroxynitrite (ONOO−) which is a highly reactive nitrogen species (RNS). High levels of ROS/RNS cause lipid peroxidation, DNA damage, interacts with both DNA repair enzymes and transcription factors, leads to the oxidation/nitration of key proteins involved in contractility, calcium handling, metabolism, antioxidant defense mechanisms, etc. It also activates the inflammatory response, Stress signals inducing cardiac hypertrophy, fibrosis, or cell death via different mechanisms (e.g., apoptosis, necrosis) and dysregulates autophagy. Therefore, the thorough understanding of the mechanisms which lead to perturbations in oxidative/Nitrative metabolism and its relationship with pro-inflammatory, hypertrophic, fibrotic, cell death and other pathways would help to develop strategies to counteract systemic and tissue oxidative/Nitrative Stress in T4CRS and renal sarcopenia. In this review, we also focus on the effects of some well-known and novel pharmaceuticals, nutraceuticals, and physical exercise on cardiac and skeletal muscle oxidative/Nitrative Stress in T4CRS and renal sarcopenia.

  • Mechanisms and Modulation of Oxidative/Nitrative Stress in Type 4 Cardio-Renal Syndrome and Renal Sarcopenia.
    Frontiers in Physiology, 2018
    Co-Authors: Marta Sarkozy, Renata Gaspar, Z A Kovacs, Monika G Kovacs, Gergő Szűcs
    Abstract:

    Chronic kidney disease (CKD) is a public health problem and a recognized risk factor for cardiovascular disease (CVD). CKD could amplify the progression of chronic heart failure leading to the development of type 4 cardio-renal syndrome (T4CRS). The severity and persistence of heart failure are strongly associated with mortality risk in T4CRS. CKD is also a catabolic state leading to renal sarcopenia which is defined as the loss of skeletal muscle strength and physical function. Renal sarcopenia also promotes the development of CVD and increases the mortality in CKD patients. In turn, heart failure developed in T4CRS could result in chronic muscle hypoperfusion and metabolic disturbances leading to or aggravating the renal sarcopenia. The interplay of multiple factors (e.g., comorbidities, the over-activated renin-angiotensin-aldosterone system [RAAS], the sympathetic nervous system [SNS], oxidative/Nitrative Stress, inflammation, etc.) may result in the progression of T4CRS and renal sarcopenia. Among these factors, oxidative/Nitrative Stress plays a crucial role in the complex pathomechanism and interrelationship between T4CRS and renal sarcopenia. In the heart and skeletal muscle, mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, uncoupled nitric oxide synthase (NOS) and xanthine oxidase are major ROS sources producing superoxide anion (O2•−) and/or hydrogen peroxide (H2O2). O2•− reacts with nitric oxide (NO) forming peroxynitrite (ONOO−) which is a highly reactive nitrogen species (RNS). High levels of ROS/RNS cause lipid peroxidation, DNA damage, interacts with both DNA repair enzymes and transcription factors, leads to the oxidation/nitration of key proteins involved in contractility, calcium handling, metabolism, antioxidant defense mechanisms, etc. It also activates the inflammatory response, Stress signals inducing cardiac hypertrophy, fibrosis, or cell death via different mechanisms (e.g., apoptosis, necrosis) and dysregulates autophagy. Therefore, the thorough understanding of the mechanisms which lead to perturbations in oxidative/Nitrative metabolism and its relationship with pro-inflammatory, hypertrophic, fibrotic, cell death and other pathways would help to develop strategies to counteract systemic and tissue oxidative/Nitrative Stress in T4CRS and renal sarcopenia. In this review, we also focus on the effects of some well-known and novel pharmaceuticals, nutraceuticals, and physical exercise on cardiac and skeletal muscle oxidative/Nitrative Stress in T4CRS and renal sarcopenia.

  • microrna 25 dependent up regulation of nadph oxidase 4 nox4 mediates hypercholesterolemia induced oxidative Nitrative Stress and subsequent dysfunction in the heart
    Journal of Molecular and Cellular Cardiology, 2013
    Co-Authors: Zoltan Varga, Krisztina Kupai, Gergő Szűcs, Renata Gaspar, Janos Paloczi, Nora Farago, Agnes Zvara, Laszlo G Puskas, Zsolt Razga
    Abstract:

    Abstract Diet-induced hypercholesterolemia leads to oxidative/Nitrative Stress and subsequent myocardial dysfunction. However, the regulatory role of microRNAs in this phenomenon is unknown. We aimed to investigate, whether hypercholesterolemia-induced myocardial microRNA alterations play a role in the development of oxidative/Nitrative Stress and in subsequent cardiac dysfunction. Male Wistar rats were fed with 2% cholesterol/0.25% cholate-enriched or standard diet for 12 weeks. Serum and tissue cholesterol levels were significantly elevated by cholesterol-enriched diet. Left ventricular end-diastolic pressure was significantly increased in cholesterol-fed rats both in vivo and in isolated perfused hearts, indicating diastolic dysfunction. Myocardial expression of microRNAs was affected by cholesterol-enriched diet as assessed by microarray analysis. MicroRNA-25 showed a significant down-regulation as detected by microarray analysis and QRT-PCR. In silico target prediction revealed NADPH oxidase 4 (NOX4) as a putative target of microRNA-25. NOX4 protein showed significant up-regulation in the hearts of cholesterol-fed rats, while NOX1 and NOX2 remained unaffected. Cholesterol-feeding significantly increased myocardial oxidative/Nitrative Stress as assessed by dihydroethidium staining, protein oxidation assay, and nitro-tyrosine ELISA, respectively. Direct binding of microRNA-25 mimic to the 3′ UTR region of NOX4 was demonstrated using a luciferase reporter assay. Transfection of a microRNA-25 mimic into primary cardiomyocytes decreased superoxide production, while a microRNA-25 inhibitor resulted in an up-regulation of NOX4 protein and an increase in oxidative Stress that was attenuated by the NADPH oxidase inhibitor diphenyleneiodonium. Here we demonstrated for the first time that hypercholesterolemia affects myocardial microRNA expression, and by down-regulating microRNA-25 increases NOX4 expression and consequently oxidative/Nitrative Stress in the heart. We conclude that hypercholesterolemia-induced microRNA alterations play an important role in the regulation of oxidative/Nitrative Stress and in consequent myocardial dysfunction.

  • MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/Nitrative Stress and subsequent dysfunction in the heart
    Journal of Molecular and Cellular Cardiology, 2013
    Co-Authors: Zoltan Varga, Krisztina Kupai, Gergő Szűcs, Renata Gaspar, Janos Paloczi, Nora Farago, Agnes Zvara, Laszlo G Puskas, Zsolt Razga, László Tiszlavicz
    Abstract:

    Abstract Diet-induced hypercholesterolemia leads to oxidative/Nitrative Stress and subsequent myocardial dysfunction. However, the regulatory role of microRNAs in this phenomenon is unknown. We aimed to investigate, whether hypercholesterolemia-induced myocardial microRNA alterations play a role in the development of oxidative/Nitrative Stress and in subsequent cardiac dysfunction. Male Wistar rats were fed with 2% cholesterol/0.25% cholate-enriched or standard diet for 12 weeks. Serum and tissue cholesterol levels were significantly elevated by cholesterol-enriched diet. Left ventricular end-diastolic pressure was significantly increased in cholesterol-fed rats both in vivo and in isolated perfused hearts, indicating diastolic dysfunction. Myocardial expression of microRNAs was affected by cholesterol-enriched diet as assessed by microarray analysis. MicroRNA-25 showed a significant down-regulation as detected by microarray analysis and QRT-PCR. In silico target prediction revealed NADPH oxidase 4 (NOX4) as a putative target of microRNA-25. NOX4 protein showed significant up-regulation in the hearts of cholesterol-fed rats, while NOX1 and NOX2 remained unaffected. Cholesterol-feeding significantly increased myocardial oxidative/Nitrative Stress as assessed by dihydroethidium staining, protein oxidation assay, and nitro-tyrosine ELISA, respectively. Direct binding of microRNA-25 mimic to the 3′ UTR region of NOX4 was demonstrated using a luciferase reporter assay. Transfection of a microRNA-25 mimic into primary cardiomyocytes decreased superoxide production, while a microRNA-25 inhibitor resulted in an up-regulation of NOX4 protein and an increase in oxidative Stress that was attenuated by the NADPH oxidase inhibitor diphenyleneiodonium. Here we demonstrated for the first time that hypercholesterolemia affects myocardial microRNA expression, and by down-regulating microRNA-25 increases NOX4 expression and consequently oxidative/Nitrative Stress in the heart. We conclude that hypercholesterolemia-induced microRNA alterations play an important role in the regulation of oxidative/Nitrative Stress and in consequent myocardial dysfunction.