CGC Bibliography Paper 5310

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

Scott BA, Avidan MS, Crowder CM

Medline:

1206745

Citation:

Science 296: 2388-2391 2002

Type:

ARTICLE

Genes:

age-1 akt-1 daf-2 daf-16 daf-18 old-1 pdk-1

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.