The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ping Liao - One of the best experts on this subject based on the ideXlab platform.
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comparison of anti oncotic effect of trpm4 blocking antibody in neuron astrocyte and vascular endothelial cell under hypoxia
Frontiers in Cell and Developmental Biology, 2020Co-Authors: Shunhui Wei, Bo Chen, See Wee Low, Charlene Priscilla Poore, Yahui Gao, Bernd Nilius, Ping LiaoAbstract:In stroke and other neurological diseases, Transient Receptor Potential Melastatin 4 (TRPM4) has been reported to cause oncotic cell death which is due to an excessive influx of sodium ions. Following stroke, hypoxia condition activates TRPM4 channel, and the sodium influx via TRPM4 is further enhanced by an increased TRPM4 expression. However, the effect of TRPM4 inhibition on oncotic cell death, particularly during the acute stage, remains largely unknown. Recently, we have developed a polyclonal antibody M4P that specifically inhibits TRPM4 channel. M4P blocks the channel via binding to a region close to the channel pore from extracellular space. Using M4P, we evaluated the acute effect of blocking TRPM4 in neurons, astrocytes, and vascular endothelial cells. In a rat stroke model, M4P co-localized with neuronal marker NeuN and endothelial marker vWF, whereas few GFAP positive astrocytes were stained by M4P in the ipsilateral hemisphere. When ATP was acutely depleted in cultured cortical neurons and microvascular endothelial cells, cell swelling was induced. Application of M4P significantly blocked TRPM4 current and attenuated Oncosis. TUNEL assay, PI staining and western blot on cleaved Caspase-3 revealed that M4P could ameliorate apoptosis after 24 h hypoxia exposure. In contrast, acute ATP depletion in cultured astrocytes failed to demonstrate an increase of cell volume, and application of M4P or control IgG had no effect on cell volume change. When TRPM4 was overexpressed in astrocytes, acute ATP depletion successfully induced Oncosis which could be suppressed by M4P treatment. Our results demonstrate that comparing to astrocytes, neurons, and vascular endothelial cells are more vulnerable to hypoxic injury. During the acute stage of stroke, blocking TRPM4 channel could protect neurons and vascular endothelial cells from oncotic cell death.
Andre Choo - One of the best experts on this subject based on the ideXlab platform.
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Excess reactive oxygen species production mediates monoclonal antibody-induced human embryonic stem cell death via Oncosis
Cell Death and Differentiation, 2017Co-Authors: Ji Yun Zheng, Heng Liang Tan, Paul Thomas Matsudaira, Andre ChooAbstract:Antibody-mediated cell killing has significantly facilitated the elimination of undesired cells in therapeutic applications. Besides the well-known Fc-dependent mechanisms, pathways of antibody-induced apoptosis were also extensively studied. However, with fewer studies reporting the ability of antibodies to evoke an alternative form of programmed cell death, Oncosis, the molecular mechanism of antibody-mediated Oncosis remains underinvestigated. In this study, a monoclonal antibody (mAb), TAG-A1 (A1), was generated to selectively kill residual undifferentiated human embryonic stem cells (hESC) so as to prevent teratoma formation upon transplantation of hESC-derived products. We revealed that A1 induces hESC death via Oncosis. Aided with high-resolution scanning electron microscopy (SEM), we uncovered nanoscale morphological changes in A1-induced hESC Oncosis, as well as A1 distribution on hESC surface. A1 induces hESC Oncosis via binding-initiated signaling cascade, most likely by ligating receptors on surface microvilli. The ability to evoke excess reactive oxygen species (ROS) production via the Nox2 isoform of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is critical in the cell death pathway. Excess ROS production occurs downstream of microvilli degradation and homotypic adhesion, but upstream of actin reorganization, plasma membrane damage and mitochondrial membrane permeabilization. To our knowledge, this is the first mechanistic model of mAb-induced Oncosis on hESC revealing a previously unrecognized role for NAPDH oxidase-derived ROS in mediating oncotic hESC death. These findings in the cell death pathway may potentially be exploited to improve the efficiency of A1 in eliminating undifferentiated hESC and to provide insights into the study of other mAb-induced cell death.
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mab 84 a cytotoxic antibody that kills undifferentiated human embryonic stem cells via Oncosis
Stem Cells, 2009Co-Authors: Heng Liang Tan, Wey Jia Fong, Eng Hin Lee, Miranda Yap, Andre ChooAbstract:The monoclonal antibody mAb 84, which binds to podocalyxin-like protein-1 (PODXL) on human embryonic stem cells (hESCs), was previously reported to bind and kill undifferentiated cells in in vitro and in vivo assays. In this study, we investigate the mechanism responsible for mAb 84-induced hESCs cytotoxicity. Apoptosis was likely not the cause of mAb 84-mediated cell death because no elevation of caspase activities or increased DNA fragmentation was observed in hESCs following incubation with mAb 84. Instead, it was preceded by cell aggregation and damage to cell membranes, resulting in the uptake of propidium iodide, and the leakage of intracellular sodium ions. Furthermore, examination of the cell surface by scanning electron microscopy revealed the presence of pores on the cell surface of mAb 84-treated cells, which was absent from the isotype control. This mechanism of cell death resembles that described for Oncosis, a form of cell death resulting from membrane damage. Additional data suggest that the binding of mAb 84 to hESCs initiates a sequence of events prior to membrane damage, consistent with Oncosis. Degradation of actin-associated proteins, namely, alpha-actinin, paxillin, and talin, was observed. The perturbation of these actin-associated proteins consequently permits the aggregation of PODXL, thus leading to the formation of pores. To our knowledge, this is the first report of oncotic cell death with hESCs as a model.
Priya Weerasinghe - One of the best experts on this subject based on the ideXlab platform.
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a model for cardiomyocyte cell death insights into mechanisms of Oncosis
Experimental and Molecular Pathology, 2013Co-Authors: Priya Weerasinghe, Sarathi Hallock, Robert E Brown, David S Loose, Maximilian L BujaAbstract:It is now known that there are at least two basic patterns of cell injury progressing to cell death: cell injury with swelling, known as Oncosis, and cell injury with shrinkage, known as apoptosis. Both types of cell death are "programmed" in the sense that the genetic information and many of the enzymes and other factors pre-exist in the cell. Previous investigation has pointed to cardiomyocyte ischemic injury evolving as the oncotic pattern of injury, although apoptosis has also been implicated. This study was designed, using a unique cell model system, to gain insight into the molecular events of anticancer agent-induced cardiomyocyte injury. Cardiomyocytes exposed for 2 h to 1.5 μg/ml sanguinarine consistently displayed the morphology of apoptosis in over 80% of cells, whereas a higher dose of 25 μg/ml at 2 h yielded the pattern of Oncosis in over 90% of cells. Microarray analysis revealed altered expression of 2514 probes in sanguinarine-induced Oncosis and 1643 probes in apoptosis at a level of significance of p<0.001. Some of the inductions such as perforin were found to be higher than 11-fold in Oncosis. When perforin was blocked by perforin-specific siRNA we found a reduction in oncotic cell death. These results strengthen the notion that Oncosis is not representative of nonspecific necrosis, but constitutes a genetically controlled form of "programmed cell death"; and also that Oncosis might represent a pathogenetic mechanism of cardiomyocyte injury. This is also the first demonstration of the involvement of perforin in cardiomyocyte Oncosis.
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Oncosis an important non apoptotic mode of cell death
Experimental and Molecular Pathology, 2012Co-Authors: Priya Weerasinghe, Maximilian L BujaAbstract:It is now increasingly accepted that apoptosis may not be the only form of cell death seen in vitro and in vivo; hence there is a need to study novel forms of cell death. The explosion of cell death research that followed the recognition of apoptosis by Kerr and colleagues in the late 1960s completely obscured the fact that apoptosis is not the only form of cell death. Apoptosis manifests itself by cell shrinkage followed by breakup; another form (Oncosis) is almost the opposite: it involves cell swelling and coagulation of the cytoplasm. The name Oncosis was chosen over a century ago by von Recklinghausen, a top collaborator of Rudolph Virchow and thereby one of the founders of cellular pathology. Nevertheless, Oncosis was forgotten, largely because a satisfactory technique for preparing tissue sections did not exist at the time. Also confusion developed regarding the distinction between Oncosis as a mode of cell injury and cell death, and necrosis as a degradation process following cell death. In this review we have described the many characteristics of Oncosis from a morphological and biochemical standpoint, and we briefly examine the application of Oncosis in disease processes.
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aurintricarboxylic acid inhibits protein synthesis independent sanguinarine induced apoptosis and Oncosis
Toxicologic Pathology, 2007Co-Authors: Sarathi Hallock, Shou Ching Tang, Maximilian L Buja, Benjamin F Trump, Andrejs Liepins, Priya WeerasingheAbstract:Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low concentration (1.5 microg/ml) induced apoptosis in K562 human erythroleukemia cells, and a high concentration (12.5 microg/ml) induced the morphology of blister formation or Oncosis-blister cell death (BCD). Treatment of cells at an intermediate sanguinarine concentration (6.25 microg/ml) induced diffuse swelling or Oncosis-diffuse cell swelling (DCS). To assess the underlying mechanism of sanguinarine-induced apoptosis and Oncosis-BCD in K562 cells, we studied their response to pre-treatment with two chemical compounds: aurintricarboxylic acid (ATA) and cycloheximide (CHX). The pretreatment effects of both chemical compounds on apoptosis and Oncosis-BCD were evaluated by measuring multiple parameters using quantitative morphology, electron microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling and annexin-V-binding. ATA, a DNA endonuclease inhibitor, efficiently prevented DNA nicking and inhibited apoptosis almost completely and Oncosis-BCD by about 40%, while CHX, a protein synthesis inhibitor, failed to inhibit both apoptosis and Oncosis-BCD. These results demonstrate, first, the importance of endonuclease in sanguinarine-induced apoptosis and to some extent in Oncosis-BCD and, second, that this inhibition does not require de novo protein synthesis.
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sanguinarine overcomes p glycoprotein mediated multidrug resistance via induction of apoptosis and Oncosis in cem vlb 1000 cells
Experimental and Toxicologic Pathology, 2006Co-Authors: Priya Weerasinghe, Sarathi Hallock, Shou Ching Tang, Benjamin Trump, Andrejs LiepinsAbstract:Abstract Permeability-glycoprotein (Pgp) positive cells are known to be encoded by the multidrug-resistance gene (MDR1), and characterized by a reduced ability to accumulate drugs. The vinblastin-resistant, Pgp positive CEM-VLB 1000 and its wild type (Pgp-negative and vinblastin-sensitive) counterpart CEM-T4 human leukemia cells, when treated with the alkaloid sanguinarine, were both found to undergo apoptosis at concentrations of 1.5 μg/ml and Oncosis/blister cell death (BCD) at concentrations of 12.5 μg/ml. The aim of this study was to assess the ability of sanguinarine to overcome Pgp-mediated multidrug-resistance (MDR), and also to characterize the cell death processes of apoptosis and Oncosis (or bimodal cell death) induced by sanguinarine in MDR cells. The cell death processes of apoptosis and Oncosis in CEM-VLB 1000 and CEM-T4 cell lines were found to be qualitatively similar when assessed by light microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling, annexin-V-binding, trypan blue exclusion and western blot analysis. Western blotting revealed an increase in the Bax/Bcl-2 ratio and activation of caspase-3 in apoptosis but not Oncosis in both cell lines. The Pgp-positive CEM-VLB 1000 cells and their wild type CEM-T4 cells were both equally sensitive to sanguinarine. Thus, sanguinarine may overcome the phenomenon of Pgp-mediated MDR by inducing apoptosis through increasing the Bax/Bcl-2 ratio and activating caspase-3, and Oncosis, which involved neither.
Jing Zhang - One of the best experts on this subject based on the ideXlab platform.
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effects of sevoflurane postconditioning on Oncosis and apoptosis in cardiomyocytes during ischemia reperfusion in isolated rat hearts relationship with erk1 2 signal transduction pathway
Chinese Journal of Anesthesiology, 2014Co-Authors: Jing Zhang, Chen Wang, Hong Xie, Jiang Zhu, Jianfang Cao, Yihui SunAbstract:Objective To evaluate the effects of sevoflurane postconditioning on the Oncosis and apoptosis in cardiomyocytes during ischemia-reperfusion (I/R) in isolated rat hearts and the role of extracellular signalregulated protein kinase 1/2 (ERK1/2) signal transduction pathway in it.Methods Seventy-two isolated rat hearts perfused in a Langendorff apparatus were randomly divided into 6 groups (n =12 each) using a random number table:sham operation group (group S),myocardial I/R group (group I/R),sevoflurane postconditioning group (group SP),PD98059 vehicle dimethyl sulfoxide (DMSO) group (group DMSO),selective ERK1/2 inhibitor PD98059 group (group PD),and sevoflurane postconditioning + PD98059 group (group SP + PD).The hearts were subjected to ischemia for 30 min followed by 2 h reperfusion in the other groups except group S.In SP,DMSO and PD groups,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane,DMSO (＜0.2％) and PD98059 (20 μmol/L),respectively,for 15 min starting from the end of ischemia until 15 min of reperfusion,and then with plain K-H solution for 105 min.In group SP+ PD,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane and PD98059 for 15 min starting from the end of ischemia until 15 min of reperfusion.Myocardial infarct size and expression of porimin and caspase-8 proteins (by Western blot) were measured at the end of reperfusion.Results Compared with S group,the myocardial infarct size was significantly increased,and the expression of porimin and caspase-8 proteins was up-regulated in the other groups (P ＜ 0.05).Compared with I/R group,the myocardial infarct size was significantly decreased,and the expression of porimin and caspase-8 proteins was down-regulated in group SP (P ＜ 0.05),and no significant changes were found in the other groups (P ＞ 0.05).Conclusion Sevoflurane postconditioning can activate ERK1/2 signal transduction pathway and inhibit the Oncosis and apoptosis in cardiomyocytes,thus attenuating I/R injury in isolated rat hearts. Key words: Anesthetics, inhalation; Myocardial reperfusion injury; Cell death; Extracellular signal-regulated MAP kinases
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effects of sevoflurane postconditioning on myocardial ischemia reperfusion induced Oncosis of cardiomyocytes in rats relationship with mitochondrial permeability transition pore
Chinese Journal of Anesthesiology, 2013Co-Authors: Ming Yin, Chen Wang, Jing Zhang, Jiang Zhu, Jianfang Cao, Peimin ChenAbstract:Objective To investigate the effects of sevoflurane postconditioning on myocardial ischemiareperfusion (I/R)-induced Oncosis of cardiomyocytes and the role of mitochondrial permeability transition pore (MPTP) in it.Methods Sixty male Sprague-Dawley rats,aged 3 months,weighing 280-360 g,were randomly divided into 5 groups (n =12 each):sham operation group (group S),group I/R,sevoflurane postconditioning group (group SP),sevoflurane postconditioning + atractyloside group (group SP + ATR) and atractyloside group (group ATR).Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 2 h reperfusion.2.5 ％ sevoflurane was inhaled for 5 min starting from 27 min of ischemia until 2 min after beginning of reperfusion in SP and SP + ATR groups,while 33 ％ oxygen was inhaled in the other groups.In SP + ATR and ATR groups,atractyloside 5 mg/kg was injected via the internal jugular vein at 15 min before ischemia.HR and systolic pressure were monitored and recorded and rate-pressure product (RPP) was calculated.At the end of reperfusion,the rats were sacrificed and the hearts removed for determination of myocardial infarct size.The myocardial ultrastrncture was observed by electron microscopy.The expression of Porimin (Pro-Oncosis receptor inducing membrane injury) was measured by Western blot.Myocardial nicotinamide adenine dinucleotide (NAD+) content was determined by spectrophotometry.Results Compared with group S,the myocardial infarct size was significantly enlarged,the expression of Porimin was up-regulated,and NAD+ content and RPP were decreased in the other four groups (P ＜ 0.05).Compared with groups I/R and SP + ATR,the infarct size was significantly decreased,the expression of Porimin was down-regulated,and NAD+ content was increased in group SP (P ＜ 0.05),and no significant change was found in the indices mentioned above in group ATR (P ＞0.05).Conclusion Sevoflurane postconditioning can mitigate myocardial I/R injury by inhibiting MPTP opening and reducing Oncosis of cardiomyocytes. Key words: Anesthetics, inhalation ; Myocardial reperfusion injury ; Cell death
Chen Wang - One of the best experts on this subject based on the ideXlab platform.
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effects of sevoflurane postconditioning on Oncosis and apoptosis in cardiomyocytes during ischemia reperfusion in isolated rat hearts relationship with erk1 2 signal transduction pathway
Chinese Journal of Anesthesiology, 2014Co-Authors: Jing Zhang, Chen Wang, Hong Xie, Jiang Zhu, Jianfang Cao, Yihui SunAbstract:Objective To evaluate the effects of sevoflurane postconditioning on the Oncosis and apoptosis in cardiomyocytes during ischemia-reperfusion (I/R) in isolated rat hearts and the role of extracellular signalregulated protein kinase 1/2 (ERK1/2) signal transduction pathway in it.Methods Seventy-two isolated rat hearts perfused in a Langendorff apparatus were randomly divided into 6 groups (n =12 each) using a random number table:sham operation group (group S),myocardial I/R group (group I/R),sevoflurane postconditioning group (group SP),PD98059 vehicle dimethyl sulfoxide (DMSO) group (group DMSO),selective ERK1/2 inhibitor PD98059 group (group PD),and sevoflurane postconditioning + PD98059 group (group SP + PD).The hearts were subjected to ischemia for 30 min followed by 2 h reperfusion in the other groups except group S.In SP,DMSO and PD groups,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane,DMSO (＜0.2％) and PD98059 (20 μmol/L),respectively,for 15 min starting from the end of ischemia until 15 min of reperfusion,and then with plain K-H solution for 105 min.In group SP+ PD,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane and PD98059 for 15 min starting from the end of ischemia until 15 min of reperfusion.Myocardial infarct size and expression of porimin and caspase-8 proteins (by Western blot) were measured at the end of reperfusion.Results Compared with S group,the myocardial infarct size was significantly increased,and the expression of porimin and caspase-8 proteins was up-regulated in the other groups (P ＜ 0.05).Compared with I/R group,the myocardial infarct size was significantly decreased,and the expression of porimin and caspase-8 proteins was down-regulated in group SP (P ＜ 0.05),and no significant changes were found in the other groups (P ＞ 0.05).Conclusion Sevoflurane postconditioning can activate ERK1/2 signal transduction pathway and inhibit the Oncosis and apoptosis in cardiomyocytes,thus attenuating I/R injury in isolated rat hearts. Key words: Anesthetics, inhalation; Myocardial reperfusion injury; Cell death; Extracellular signal-regulated MAP kinases
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effects of sevoflurane postconditioning on myocardial ischemia reperfusion induced Oncosis of cardiomyocytes in rats relationship with mitochondrial permeability transition pore
Chinese Journal of Anesthesiology, 2013Co-Authors: Ming Yin, Chen Wang, Jing Zhang, Jiang Zhu, Jianfang Cao, Peimin ChenAbstract:Objective To investigate the effects of sevoflurane postconditioning on myocardial ischemiareperfusion (I/R)-induced Oncosis of cardiomyocytes and the role of mitochondrial permeability transition pore (MPTP) in it.Methods Sixty male Sprague-Dawley rats,aged 3 months,weighing 280-360 g,were randomly divided into 5 groups (n =12 each):sham operation group (group S),group I/R,sevoflurane postconditioning group (group SP),sevoflurane postconditioning + atractyloside group (group SP + ATR) and atractyloside group (group ATR).Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 2 h reperfusion.2.5 ％ sevoflurane was inhaled for 5 min starting from 27 min of ischemia until 2 min after beginning of reperfusion in SP and SP + ATR groups,while 33 ％ oxygen was inhaled in the other groups.In SP + ATR and ATR groups,atractyloside 5 mg/kg was injected via the internal jugular vein at 15 min before ischemia.HR and systolic pressure were monitored and recorded and rate-pressure product (RPP) was calculated.At the end of reperfusion,the rats were sacrificed and the hearts removed for determination of myocardial infarct size.The myocardial ultrastrncture was observed by electron microscopy.The expression of Porimin (Pro-Oncosis receptor inducing membrane injury) was measured by Western blot.Myocardial nicotinamide adenine dinucleotide (NAD+) content was determined by spectrophotometry.Results Compared with group S,the myocardial infarct size was significantly enlarged,the expression of Porimin was up-regulated,and NAD+ content and RPP were decreased in the other four groups (P ＜ 0.05).Compared with groups I/R and SP + ATR,the infarct size was significantly decreased,the expression of Porimin was down-regulated,and NAD+ content was increased in group SP (P ＜ 0.05),and no significant change was found in the indices mentioned above in group ATR (P ＞0.05).Conclusion Sevoflurane postconditioning can mitigate myocardial I/R injury by inhibiting MPTP opening and reducing Oncosis of cardiomyocytes. Key words: Anesthetics, inhalation ; Myocardial reperfusion injury ; Cell death
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the role of Oncosis in mycardial ischemia reperfusion injury
International Journal of Anesthesiology and Resuscitation, 2013Co-Authors: Xiuli Jiang, Chen WangAbstract:Background Onconsis and apoptosis may occur in mycardial ischemia/reperfusion injury (I/RI).Onconsis is a special model of non-apoptotic cell death.It is characterized by cell swelling,blistering,organelles swelling,cell membrane permeability and caryolysis.Objective Understanding the role of Oncosis occurs in myocardial ischemia/reperfusion(I/R) may help us understand the myocardial protection research.Content The role of Oncosis in the biological characteristics mechanism and in myocardial I/RI were reviewed in this article.Trend New breakthrough in myocardial protection may be found by understanding myocardial cell Oncosis. Key words: Onconsis; Apoptosis; Mycardial reperfusion injury
