Hypoxia induces the expression of the pro-apoptotic gene BNIP3.
It has been shown that oxygen deprivation results in apoptotic cell death, and that hypoxia inducible factor 1 (HIF1) and the tumor suppressor p53 play key roles in this process. However, the molecular mechanism through which hypoxia and HIF1 induce apoptosis is not clear. Here we show that the expression of pro-apoptotic gene BNIP3 is dramatically induced by hypoxia in various cell types, including primary rat neonatal cardiomyocytes. Overexpression of HIF1alpha, but not p53, induces the expression of BNIP3. Overexpression of BNIP3 leads to a rather unusual type of apoptosis, as no cytochrome c leakage from mitochondria was detected and inhibitors of caspases were unable to prevent cell death. Taken together, these data suggest that HIF1-dependent induction of BNIP3 may play a significant role during hypoxia-induced cell death.
Guo
K
K
Cardiovascular Biology, Aventis Pharma, Room 245, Industriepark Hochst, H825, 65926 Frankfurt a. Main, Germany.
Searfoss
G
G
Krolikowski
D
D
Pagnoni
M
M
Franks
C
C
Clark
K
K
Yu
K T
KT
Jaye
M
M
Ivashchenko
Y
Y
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000502:physiology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins
C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases