The endoplasmic reticulum (ER)-target protein Bik induces Hep3B cells apoptosis by the depletion of the ER Ca2+ stores.
Bik, a BH3-only protein, was identified to induce cells apoptosis. In this study, we reported that Bik exclusively localized to endoplasmic reticulum rather than mitochondria. The apoptosis induced by Bik was inhibited in Hep3B cells, when TM domain of Bik was truncated. The ectopic overexpression of Bik protein caused the rapid and sustained elevation of the intracellular cytosolic Ca2+, which originated from the ER Ca2+ stores releasing. The Hep3B cells apoptosis induced by Bik was not prevented by establishing the clamped cytosolic Ca2+ condition, or by buffering of the extracellular Ca2+ with EGTA, suggesting that the depletion of ER Ca2+ stores rather than the elevation of cytosolic Ca2+ or the extracellular Ca2+ entry contributed to Bik-induced Hep3B cells apoptosis.
Zhao
Xiaoping
X
Department of Biochemistry and Molecular Biology, School of Medicine, Shanghai Jiao Tong University, Research Center for Human Gene Therapy, No. 280 Chongqing Road South, and Department of Gastroenterology, Ruijin Hospital, Shanghai 200025, China.
Wang
Li
L
Sun
Yan
Y
Ye
Ling
L
Lu
Jian
J
Yuan
Yaozong
Y
Qian
Guanxiang
G
Ge
Shengfang
S
D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins; D017434:Protein Structure, Tertiary / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D002118:Calcium