bcl-2/Adenovirus E1B 19-kd interacting protein 3 (BNIP3) regulates hypoxia-induced neural precursor cell death.
Abstract
Perinatal hypoxia-ischemia may result in long-term neurological deficits. In addition to producing neuron death, HI causes death of neural precursor cells (NPCs) in the developing brain. To characterize the molecular pathways that regulate hypoxia-induced death of NPCs, we treated a mouse neural stem cell line (C17.2 cells) and fibroblastic growth factor II-expanded primary NPCs derived from wild-type or gene-disrupted mice, with oxygen glucose deprivation or the hypoxia mimetics desferrioxamine or cobalt chloride. Neural precursor cells undergoing hypoxia exhibited time- and concentration-dependent caspase-3 activation and cell death, which was significantly reduced by treatment with a broad caspase inhibitor or protein synthesis inhibition. Bax/Bak-deficient NPCs were protected from desferrioxamine-induced death and exhibited minimal caspase-3 activation. Oxygen glucose deprivation or hypoxia-mimetic exposure also resulted in increased hypoxia-inducible factor alpha and bcl-2/adenovirus E1B 19-kd interacting protein 3 (BNIP3) expression. BNIP3 shRNA treatment failed to affect hypoxia-induced caspase-3 activation but inhibited cell death and nuclear translocation of apoptosis-inducing factor, indicating that BNIP3 is an import...Continue Reading
References
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing
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