Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2.

Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science (Impact Factor: 31.48). 07/2002; 296(5577):2388-91. DOI: 10.1126/science.1072302
Source: PubMed

ABSTRACT To identify genetic determinants of hypoxic cell death, we screened for hypoxia-resistant (Hyp) mutants in Caenorhabditis elegans and found that specific reduction-of-function (rf) mutants of daf-2, an insulin/insulinlike growth factor (IGF) receptor (INR) homolog gene, were profoundly Hyp. The hypoxia resistance was acutely inducible just before hypoxic exposure and was mediated through an AKT-1/PDK-1/forkhead transcription factor pathway overlapping with but distinct from signaling pathways regulating life-span and stress resistance. Selective neuronal and muscle expression of daf-2(+) restored hypoxic death, and daf-2(rf) prevented hypoxia-induced muscle and neuronal cell death, which demonstrates a potential for INR modulation in prophylaxis against hypoxic injury of neurons and myocytes.

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