Programmed cell death(PCD)is mediated by specific genes that encode signals.It can balance cell survival and death.Pyroptosis is a type of inflammatory,caspase-dependent PCD mediated by gasdermin proteins,which functi...Programmed cell death(PCD)is mediated by specific genes that encode signals.It can balance cell survival and death.Pyroptosis is a type of inflammatory,caspase-dependent PCD mediated by gasdermin proteins,which function in pore formation,cell expansion,and plasma membrane rupture,followed by the release of intracellular contents.Pyroptosis is mediated by caspase-1/3/4/5/11 and is primarily divided into the classical pathway,which is dependent on caspase-1,and the non-classical pathway,which is dependent on caspase-4/5/11.Inflam-masomes play a vital role in these processes.The various components of the pyroptosis pathway are related to the occurrence,invasion,and metastasis of tumors.Research on pyroptosis has revealed new options for tumor treatment.This article summarizes the recent research progress on the molecular mechanism of pyroptosis,the relationship between the various components of the pyroptosis pathway and cancer,and the applications and prospects of pyroptosis in anticancer therapy.展开更多
We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-...We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase（PERK）, eukaryotic initiation factor 2-alpha（eIF2α） and activating transcription factor 4（ATF4）. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone（0.1, 1, 10, 100 μM） treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated（p）-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.展开更多
文摘Programmed cell death(PCD)is mediated by specific genes that encode signals.It can balance cell survival and death.Pyroptosis is a type of inflammatory,caspase-dependent PCD mediated by gasdermin proteins,which function in pore formation,cell expansion,and plasma membrane rupture,followed by the release of intracellular contents.Pyroptosis is mediated by caspase-1/3/4/5/11 and is primarily divided into the classical pathway,which is dependent on caspase-1,and the non-classical pathway,which is dependent on caspase-4/5/11.Inflam-masomes play a vital role in these processes.The various components of the pyroptosis pathway are related to the occurrence,invasion,and metastasis of tumors.Research on pyroptosis has revealed new options for tumor treatment.This article summarizes the recent research progress on the molecular mechanism of pyroptosis,the relationship between the various components of the pyroptosis pathway and cancer,and the applications and prospects of pyroptosis in anticancer therapy.
基金supported by a grant from the Science&Technology Bureau of Changzhou City of China,No.CJ20130029
文摘We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase（PERK）, eukaryotic initiation factor 2-alpha（eIF2α） and activating transcription factor 4（ATF4）. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone（0.1, 1, 10, 100 μM） treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated（p）-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.
