Endoplasmic reticulum mediated necrosis-like apoptosis of HeLa cells induced by Ca2+ oscillation.
Apoptosis and necrosis are distinguished by modality primarily. Here we show an apoptosis occurred instantly, induced by 300 muM W-7 ((N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride), inhibitor of calmodulin), which demonstrated necrotic modality. As early as 30 min after W-7 addition, apoptotic (sub-diploid) peak could be detected by fluorescence-activated cell sorter (FACS), "DNA ladders" began to emerge also at this time point, activity of caspase-3 elevated obviously within this period. Absence of mitochondrial membrane potential (MMP) reduction and cytochrome c, AIF (apoptosis inducing factor) release, verified that this rapid apoptosis did not proceed through mitochondria pathway. Activation of caspase-12 and changes of other endoplasmic reticulum (ER) located proteins ascertained that ER pathway mediated this necrosis-like apoptosis. Our findings suggest that it is not credible to judge apoptosis by modality. Elucidation of ER pathway is helpful to comprehend the pathology of diseases associated with ER stress, and may offer a new approach to the therapy of cancer and neurodegenerative diseases.
Hu
Qingliu
Q
Medical School, Tsinghua University, Beijing 100084, People's Republic of China.
Chang
Junlei
J
Tao
Litao
L
Yan
Guoliang
G
Xie
Mingchao
M
Wang
Zhao
Z
D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D053454:Caspase 12 / Q000378:metabolism; D002469:Cell Separation; D045304:Cytochromes c / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D009991:Oscillometry
D051033:Apoptosis Inducing Factor; D045304:Cytochromes c; D004247:DNA; D053454:Caspase 12; D002118:Calcium