Dephosphorylation of cell cycle-regulated proteins correlates with anoxia-induced suspended animation in Caenorhabditis elegans.
Some metazoans have evolved the capacity to survive severe oxygen deprivation. The nematode, Caenorhabditis elegans, exposed to anoxia (0 kPa, 0% O(2)) 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.
Padilla
Pamela A
PA
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Nystul
Todd G
TG
Zager
Richard A
RA
Johnson
Ali C M
AC
Roth
Mark B
MB
D000222:Adaptation, Physiological; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000705:Anaphase / Q000502:physiology; D000818:Animals; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000939:Epitopes / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D014157:Transcription Factors
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D000939:Epitopes; D051793:Hypoxia-Inducible Factor 1; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010100:Oxygen