Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans.
Oxygen deprivation is a major cause of cellular damage and death. Here we demonstrate that Caenorhabditis elegans embryos, which can survive both in anoxia (<0.001 kPa O(2)) by entering into suspended animation and in mild hypoxia (0.25-1 kPa O(2)) through a hypoxia-inducible factor 1-mediated response, cannot survive in intermediate concentrations of oxygen, between 0.01 and 0.1 kPa O(2). Moreover, we show that carbon monoxide can protect C. elegans embryos against hypoxic damage in this sensitive range. Carbon monoxide can also rescue the hypoxia-sensitive mutant hif-1(ia04) from lethality in hypoxia. This work defines the oxygen tensions over which hypoxic damage occurs in C. elegans embryos and demonstrates that carbon monoxide can prevent this damage by inducing suspended animation.
Nystul
Todd G
TG
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98105, USA.
Roth
Mark B
MB
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D002248:Carbon Monoxide / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D009687:Nuclear Proteins / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity; D016019:Survival Analysis; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D009687:Nuclear Proteins; D014157:Transcription Factors; D002248:Carbon Monoxide; D010100:Oxygen