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A more recent version of this article appeared on May 1, 2002
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Submitted on December 26, 2001
Revised on February 7, 2002
Accepted on February 14, 2002
1 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
2 Division of Basic Sciences, and Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
3 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
4 Division of Basic Sciences, Molecular and Cellular Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
* Corresponding author. E-mail address: mroth{at}fred.fhcrc.org.
Some metazoans have evolved the capacity to survive severe oxygen deprivation. The nematode, Caenorhabditis elegans, exposed to anoxia (0 kPa, 0% O2) enters into a recoverable state of suspended animation during all stages of the life cycle. That is, all microscopically observable movement ceases including cell division, developmental progression, feeding, and motility. To understand suspended animation we compared oxygen-deprived embryos to non-treated embryos in both wild-type and hif-1 mutants. We found that hif-1 mutants survive anoxia, suggesting that the mechanisms for anoxia survival are different than those required for hypoxia. Examination of wild-type embryos exposed to anoxia show that blastomeres arrest in interphase, prophase, metaphase, and telophase but not anaphase. Analysis of the energetic state of anoxic embryos indicated a reversible-depression in the ATP to ADP ratio. Given that a decrease in ATP concentrations likely affects a variety of cellular processes, including signal transduction, we compared the phosphorylation state of several proteins in anoxic embryos and normoxic embryos. We found that the phosphorylation state of histone H3 and cell cycle regulated proteins recognized by the MPM-2 antibody were not detectable in anoxic embryos. Thus, dephosphorylation of specific proteins correlate with the establishment and/or maintenance of a state of anoxia-induced suspended animation.
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