Sci. Aging Knowl. Environ., 19 June 2002
Regulation of Hypoxic Death in C. elegans by the Insulin/IGF Receptor Homolog DAF-2
Barbara A. Scott, Michael S. Avidan, and C. Michael Crowderhttp://sageke.sciencemag.org/cgi/content/abstract/sageke;2002/24/or6
Abstract: Science 13 June 2002 (10.1126/science.1072302) (Science Express Reports)
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/IGF receptor (INR) homolog gene, were profoundly Hyp. The hypoxia resistance was acutely inducible just prior to 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, demonstrating the potential for INR modulation in prophylaxis against hypoxic injury of neurons and myocytes.
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