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Originally published in Science Express on 13 June 2002
Science 28 June 2002:
Vol. 296. no. 5577, pp. 2388 - 2391
DOI: 10.1126/science.1072302
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Reports

Regulation of Hypoxic Death in C. elegans by the Insulin/IGF Receptor Homolog DAF-2

Barbara A. Scott,1 Michael S. Avidan,1 C. Michael Crowder12*

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.

1 Department of Anesthesiology, and
2 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed. E-mail: crowderm{at}morpheus.wustl.edu

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