This effect was independent from expression of pro. Nuclear translocation of the mitochondrial flavoprotein apoptosisinducing factor aif might be key to one such pathway, but. The kit contains enough primary and secondary antibodies to perform 10 western mini blots, as well as a. A caspaseindependent apoptosis pathway springerlink. However, little is known about the mechanistic basis for its anticancer activity. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Boswellic acids trigger apoptosis via a pathway dependent on.
Activation of the caspase3 pathway is a hallmark of apoptosis and can be used in cellular assays to quantify activators and inhibitors of the death cascade. Joza et al deleted exon 3 of the aif gene in mouse embryonic stem es cells. This difference suggests that both caspase 9, caspase 3dependent fig. Oct 10, 2008 pathways to caspase 3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c release and caspase 9 function. Induction of apoptotic dna fragmentation mediated by. The mammalian lignan enterolactone is a major metabolite of plantbased lignans that has been shown to inhibit the growth and development of prostate cancer. Caspase3 activation by lysosomal enzymes in cytochrome c. Caspase 3 dependent and independent pathways article pdf available in journal of pharmacology and experimental therapeutics 3021. Leptospira interrogans induces apoptosis in macrophages.
Pdf caspase3independent apoptotic pathways contribute. Mammalian ste20like protein kinase 3 induces a caspase. The present study found that all three curcuminoids cur, dmc and bdmc are equipotent in inducing hos cell apoptosis by caspasedependent and independent pathways through activation of smad23 and repression of akt signaling pathway. M induced oxidative stress in rat proximal tubular rpt cells, as seen in the reactive oxygen species levels. Caspase 3 independent apoptotic pathways contribute to interleukin32. However, even in the absence of caspase 3 activation, a2780 cells do exhibit some morphological characteristics of cisplatininduced apoptosis, including a subset of the biochemical features of pcd. Induction of cell death following reovirus infection is initiated by the incoming viral capsid proteins during cell entry and occurs via nf. However, the mechanism of caspase3 activation in cytochrome cindependent apoptosis remains to be clarified. Pathways to caspase3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c release and caspase9 function. In the present study, we showed that evodiamine activated the caspase dependent apoptotic pathway. The present study found that all three curcuminoids cur, dmc and bdmc are equipotent in inducing hos cell apoptosis by caspase dependent and independent pathways through activation of smad2 3 and repression of akt signaling pathway.
Downstream pathways of mst1 in the induction of apoptosis remain to be clarified. A neutrophil spontaneous death was caspase dependent. Culture in the presence of caffeine resulted in a strong sensitization for p14 arf. Abrogation of caspase 3 activity resulted in the reduction but not the abrogation of apoptotic dna fragmentation fig. Brain morphology in caspase 9mice was more aberrant than in caspase 3 mice. Caspase 3 independent forms of apoptosis have received increasing recognition, including those triggered by lysosome proteases known as cathepsins and by apoptosis inducing factor aif. In this study, we used cellular models to mimic such blockade. Effect of glutathione depletion on caspase 3 independent apoptosis pathway induced by curcumin in jurkat cells. However, even in the absence of caspase3 activation, a2780 cells do exhibit some morphological characteristics of cisplatininduced apoptosis, including a subset of the biochemical features of pcd. Both caspase9 and caspase8 are defined as initiator caspases and can in turn activate caspase3, the executor of apoptosis 22, 23. Furthermore, a pancaspase inhibitor blocked apoptosis and activation of both caspases3 and 8. Results in this study, we found that the expression of mst1 resulted in caspase. Atp induces caspase3gasdermin emediated pyroptosis in. The response is both time and concentration dependent, suggesting that multiple pathways play a role in triggering the caspase3 activation.
This exon encodes the amino terminus of the protein, and because the aif gene is on the x chromosome, mutation of one aif allele resulted in a complete knockout in male es cells. Rosdependent baxbcl2 and caspase 3 pathway mediated apoptosis induced by zineb in human keratinocyte cells daoud ali,1 abhilasha tripathi,2 hussain al ali, 3 yadvendra shahi,2 kamlesh k mishra,2 saud alarifi,1 abdullah a alkahtane,1 salem manohardas1 1department of zoology, science college, king saud university, riyadh, saudi arabia. Most anticancer agents eradicate tumor cells by the induction of apoptosis. The role of mitochondria and apical caspases in apoptosis induced by the benzene metabolite hydroquinone hq remains to be elucidated.
Nuclear translocation of the mitochondrial flavoprotein apoptosis inducing factor aif might be key to one such pathway, but. The resulting mutant cells were defective in apoptosis. Caspase 9mice often developed brain tissue outside the skull. Figure1 classic programmed cell death pcd involves activation of caspases. Environmental chemicalinduced bone marrow b cell apoptosis. In this study, we report that enterolactone selectively suppresses the growth of lncap prostate cancer cells by triggering. Jul 26, 2016 finally, ssd also increases the release of apoptotic factors. Prototype reovirus strain t3d displays a higher cellkilling potential than strain t1l.
These results suggest a complex death receptorindependent b cell apoptosis pathway in which caspase8 is activated downstream of caspase3. Inhibition of caspase3 blocked caspase8 activation and apoptosis. Interestingly, application of the caspase 9 inhibitor potentiated. Recently, it was found that the cross communication exists between the two pathways, as caspase 8 may activate caspase 9 via bid, a member of bcl2 family 24. Recent studies have suggested that the various anticancer agents used against cancer mediate their effects by induction of apoptosis of the cancer cells. Caspase3independent apoptotic pathways contribute to. Apoptosis is induced by radiofrequency fields through the caspaseindependent mitochondrial pathway in cortical neurons. Virusinduced apoptosis is thought to be the primary mechanism of cell death following reovirus infection. Although aif is a flavoprotein normally found in mitochondria, it mediates apoptosis by a caspase independent mechanism 10, 11. Caspases are crucial mediators of programmed cell death apoptosis. Alternative models of programmed cell death pcd have therefore been proposed. In this report, mst3 was found to play an essential role in staurosporineinduced apoptosis by triggering both caspasedependent and independent pathways. We designed this study to investigate whether cadmium induces caspaseindependent apoptosis and to investigate the relationship between the caspasedependent and caspaseindependent apoptotic pathways. Thus caspase 8 activation by menadione is independent of the activity of caspase 9 and caspase 3, as well as of the mptp opening.
Among them, caspase3 is a frequently activated death protease, catalyzing the specific cleavage of many key cellular proteins. Enterolactone induces apoptosis in human prostate carcinoma. Boswellic acids trigger apoptosis via a pathway dependent. Increasing evidence, however, suggests that caspaseindependent pathways also exist. The overall analytical data indicate that ssdelicited cell death may occur through caspase3dependent, caspase3independent and mitochondrial pathways in mammalian hscs, and thus can delay the formation of liver fibrosis by reducing the level of hscs. In addition to its function in regulating apoptosis, we show that b56. Although aif is a flavoprotein normally found in mitochondria, it mediates apoptosis by a caspaseindependent mechanism 10,11. Bdependent activation of classical apoptotic pathways. However, there is now accumulating evidence indicating that cell death can occur in a programmed fashion but in complete absence and independent of caspase activation.
Emerging roles of caspase3 in apoptosis cell death. Simple explanation of the mechanisms of apoptosis triggered by internal signals bcl2, along the caspase 9, caspase 3 and caspase 7 pathway. Simple explanation of the mechanisms of apoptosis triggered by internal signals bcl2, along the caspase9, caspase3 and caspase7 pathway. Thus caspase8 activation by menadione is independent of the activity of caspase9 and caspase3, as well as of the mptp opening. Prototype reovirus strain t3d displays a higher cellkilling. Pdf neural cell apoptosis induced by microwave exposure.
Previously kuida et al demonstrated a caspase 9 dependent and caspase 3 independent apoptotic pathway, since thymocytes from caspase 9mice are resistant to gamma irradiation and dexamethasone, whereas thymocytes from caspase 3 mice are sensitive, suggesting that other caspases are directly activated by caspase 9. Caspase3independent forms of apoptosis have received increasing recognition, including those triggered by lysosome proteases known as cathepsins and by apoptosisinducing factor aif. Pdf a traditional poly herbal drug induced apoptosis via. Reovirus activates a caspaseindependent cell death pathway. Recently, it was found that the cross communication exists between the two pathways, as caspase8 may activate caspase9 via bid, a member of bcl2 family 24. Caspase3 activation during neutrophil spontaneous death is independent of caspase8 or caspase9.
Cisplatininduced apoptosis proceeds by caspase3dependent. A traditional poly herbal drug induced apoptosis via caspase 3 mediated pathway in rd cells but caspase 3 independent pathway in mcf7 cells article information article pdf available october. In this report, mst3 was found to play an essential role in staurosporineinduced apoptosis by triggering both caspase dependent and independent pathways. Pdf caspase3independent apoptotic pathways contribute to. The characterization of the caspases allowed the development of caspase inhibitors, which can be used to determine whether a cellular process involves active caspases.
Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced. Caspase 3 has been found to be necessary for normal brain development as well as its typical role in apoptosis, where it is responsible for chromatin condensation and dna fragmentation. Further studies show that mst3 may trigger a caspaseindependent apoptotic pathway by regulating the nuclear translocation of aif and endog and the dnase activity associated with endog. Caspasedependent and caspaseindependent apoptosis induced. Caspaseindependent apoptosis the eyes have it journal of. Patterns of cell death have been divided into apoptosis, which is actively executed by specific proteases, the caspases, and accidental necrosis. Full text rosdependent baxbcl2 and caspase 3 pathway. May 17, 20 this effect was independent from expression of pro.
Caspase8mediated apoptosis induced by oxidative stress. Our findings suggest that during etoposideinduced apoptosis, caspase 3 is activated by a pathway independent of cytochrome c in p39 cells. Abrogation of caspase3 activity resulted in the reduction but not the abrogation of apoptotic dna fragmentation fig. It remains unclear whether atp can induce pyroptosis in macrophages when the nlrp3 pathway is blocked by pathogenic infection. Oxidative stress promotes apoptosis in primary rpt cell cultures exposed to cadmium 5, 25 and exploring the role of the mitochondrial apoptosis pathway, the caspase dependent and caspase independent apoptotic pathways, and the relationship between the two in rpt cell apoptosis, is necessary. However, the mechanism of caspase 3 activation in cytochrome c independent apoptosis remains to be clarified. Saikosaponin d induces cell death through caspase3dependent. Amphibian frog xenopus laevis serves as an ideal model system for the study of the mechanisms of apoptosis.
Intrinsic pathway of hydroquinone induced apoptosis occurs. Atp acts as a canonical activator to induce nlrp3 nodlike receptor family, pyrin domain containing 3 inflammasome activation in macrophages, leading to caspase 1gasdermin d gsdmdmediated pyroptosis. Here, we investigated the involvement of mitochondria and activation of the apical caspases8 and 9 in hq induced apoptosis in myeloperoxidase mporich hl60 and mpodeficient jurkat t cells. The results thus far suggest that cp70 and c30 cells initiate apoptosis via a caspase3dependent pathway. Leptospira interrogans induces apoptosis in macrophages via. It is suggested that there are several apoptotic pathways in cells responsive to apoptotic stimuli, such as the death. Caspase3independent apoptotic pathways contribute to interleukin32. This antibody does not recognize full length caspase 3 or other cleaved caspases. Apoptosis is induced by radiofrequency fields through the. Caspases at the us national library of medicine medical subject headings. Cleaved caspase3 asp175 western detection kit offers an efficient way of detecting caspase3 processing and activation by western blotting. Interestingly, application of the caspase9 inhibitor potentiated.
Further studies show that mst3 may trigger a caspase independent apoptotic pathway by regulating the nuclear translocation of aif and endog and the dnase activity associated with endog. Atp acts as a canonical activator to induce nlrp3 nodlike receptor family, pyrin domain containing 3 inflammasome activation in macrophages, leading to caspase1gasdermin d gsdmdmediated pyroptosis. Increasing evidence, however, suggests that caspase independent pathways also exist. Apoptosis was preceded by cleavage of caspase3 46 h and caspase8 68 h and their respective substrates. Cells from mice defective in tumor necrosis factor tnf. During apoptosis, caspase cleavage of mst1 removes a c. Thus, our findings suggest that the mitochondrialmediated, caspase dependent pathway is one possible mechanism underscoring enterolactoneinduced apoptosis. Therefore, the p53induced cell death program in the presence of zvad appears to differ from most caspase independent alternative pathways. Caspase 3 antibody detects endogenous levels of full length caspase 3 35 kda and the large fragment of caspase 3 resulting from cleavage 17 kda. There also exists a caspase independent apoptotic pathway that is mediated by aif apoptosis inducing factor. Saikosaponin d induces cell death through caspase3. Therefore, the p53induced cell death program in the presence of zvad appears to differ from most caspaseindependent alternative pathways. The results thus far suggest that cp70 and c30 cells initiate apoptosis via a caspase 3 dependent pathway. Caspaseindependent apoptosis the eyes have it journal.
In the present study, we investigated whether continuouswave cw radiofrequency rf fields induce neuron apoptosis in vitro. Elevated levels of a fragment of caspase 3, p17, in the bloodstream is a sign of a recent myocardial infarction. Effect of glutathione depletion on caspase3 independent apoptosis pathway induced by curcumin in jurkat cells. Caspase8mediated apoptosis induced by oxidative stress is. Finally, ssd also increases the release of apoptotic factors. Among them, caspase 3 is a frequently activated death protease, catalyzing the specific cleavage of many key cellular proteins. Both caspase 9 and caspase 8 are defined as initiator caspases and can in turn activate caspase 3, the executor of apoptosis 22, 23. Previously kuida et al demonstrated a caspase9 dependent and caspase3 independent apoptotic pathway, since thymocytes from caspase9mice are resistant to gamma irradiation and dexamethasone, whereas thymocytes from caspase3mice are sensitive, suggesting that other caspases are directly activated by caspase9. Rosdependent baxbcl2 and caspase 3 pathwaymediated apoptosis induced by zineb in human keratinocyte cells daoud ali,1 abhilasha tripathi,2 hussain al ali,3 yadvendra shahi,2 kamlesh k mishra,2 saud alarifi,1 abdullah a alkahtane,1 salem manohardas1 1department of zoology, science college, king saud university, riyadh, saudi arabia. This apoptosis was only partially inhibited by a pancaspase inhibitor benzyloxycarbonylvalalaaspfluoromethyl ketone, which suggested that evodiamineinduced apoptosis in leukemic u937 cells is partially caspase independent.
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