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Vol. 13, Issue 5, 1473-1483, May 2002


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*Division of Basic Sciences, 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
nontreated 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 from 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.
Molecular and Cellular
Biology Program,
Clinical Research Division, Fred
Hutchinson Cancer Research Center, Seattle, Washington 98109
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