The guanosine monophosphate reductase gene is conserved in rats and its expression increases rapidly in brown adipose tissue during cold exposure.
Non-shivering thermogenesis is required for survival of rodents during cold stress. Uncoupling protein-1 acts in brown adipose tissue (BAT) to transport protons, thus dissipating the proton gradient across the inner mitochondrial membrane. This permits respiration uncoupled from ATP synthesis. UCP-1 function is inhibited by the binding of purine nucleotides, with GTP/GDP being more potent than ATP/ADP. We used a cDNA subtraction analysis to identify cDNAs rapidly induced by cold exposure. One of these encodes rat guanosine monophosphate reductase (GMP-r). This was surprising in that previous data had suggested that this enzyme was absent in rodents. Rat GMP-r is 96% identical to human GMP-r, and its mRNA is increased 30-fold in BAT within 6 h of cold exposure. The gene is also expressed (but not cold-responsive) in muscle and kidney, but not in white fat. We speculate that the physiological function of the marked increase in BAT GMP-r during cold stress may be to deplete the brown adipocyte of guanine nucleotides, converting them to IMP, thus permitting enhanced UCP-1 function. This is a previously unrecognized regulatory aspect of thermogenesis, an essential physiological response of rodents to cold.
Salvatore
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Thyroid Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Bartha
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Larsen
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PR
D000064:Acclimatization / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001833:Body Temperature Regulation / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D003080:Cold Temperature; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D050899:GMP Reductase; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D015723:Gene Library; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D013961:Thyroid Gland / Q000502:physiology; D014475:Uncoupling Agents / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D018076:DNA, Complementary; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604373:Ucp1 protein, rat; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D009247:NADH, NADPH Oxidoreductases; D050899:GMP Reductase