Hydrogen sulfide increases hypoxia-inducible factor-1 activity independently of von Hippel-Lindau tumor suppressor-1 in C. elegans.
Rapid alteration of gene expression in response to environmental changes is essential for normal development and behavior. The transcription factor hypoxia-inducible factor (HIF)-1 is well known to respond to alterations in oxygen availability. In nature, low oxygen environments are often found to contain high levels of hydrogen sulfide (H(2)S). Here, we show that Caenorhabditis elegans can have mutually exclusive responses to H(2)S and hypoxia, both involving HIF-1. Specifically, H(2)S results in HIF-1 activity throughout the hypodermis, whereas hypoxia causes HIF-1 activity in the gut as judged by a reporter for HIF-1 activity. C. elegans require hif-1 to survive in room air containing trace amounts of H(2)S. Exposure to H(2)S results in HIF-1 nuclear localization and transcription of HIF-1 targets. The effects of H(2)S on HIF-1 reporter activity are independent of von Hippel-Lindau tumor suppressor (VHL)-1, whereas VHL-1 is required for hypoxic regulation of HIF-1 reporter activity. Because H(2)S is naturally produced by animal cells, our results suggest that endogenous H(2)S may influence HIF-1 activity.
Budde
Mark W
MW
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA.
Roth
Mark B
MB
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D044842:Cullin Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016019:Survival Analysis
D029742:Caenorhabditis elegans Proteins; D044842:Cullin Proteins; D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C541177:VHL-1 protein, C elegans; D049452:Green Fluorescent Proteins; D006862:Hydrogen Sulfide