Nitric oxide-induced suspended animation promotes survival during hypoxia.
Oxygen plays a key role in energy metabolism. However, there are organisms that survive severe shortfalls in oxygen. Drosophila embryos rapidly arrest development upon severe hypoxia and recover upon restoration of oxygen, even days later. Stabilization of the normally unstable engrailed RNA and protein preserved the localized striped pattern of this embryonic patterning gene during 3 days in hypoxia. Severe hypoxia blocked expression of a heat-shock-inducible lacZ transgene. Cyanide, a metabolic poison, did not immediately block gene expression or turnover, arguing against a passive response to energy limitation. In contrast, nitric oxide, a putative hypoxia signal, induced a reversible arrest of development, gene expression and turnover. Reciprocally, a nitric oxide scavenger allowed continued gene expression and turnover during hypoxia, but it reduced hypoxia tolerance. We suggest that hypoxia-induced stasis preserves the status quo of embryonic processes and promotes survival. Our data implicate nitric oxide as a mediator of this response and provide a system in which to investigate its action.
Teodoro
Rita O
RO
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0448, USA.
O'Farrell
Patrick H
PH
D000818:Animals; D019521:Body Patterning; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000502:physiology; D004579:Electron Transport / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia; D007093:Imidazoles / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D019076:Transgenes
D003497:Cyclic N-Oxides; D029721:Drosophila Proteins; C063459:En protein, Drosophila; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D018398:Homeodomain Proteins; D007093:Imidazoles; D020030:Nitric Oxide Donors; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D014157:Transcription Factors; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D003609:Dactinomycin; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D003513:Cycloheximide; D012966:Sodium Cyanide; D010100:Oxygen