The Guanosine Monophosphate Reductase Gene Is Conserved in Rats and Its Expression Increases Rapidly in Brown Adipose Tissue during Cold Exposure

作者: Domenico Salvatore , Tibor Bartha , P. Reed Larsen

DOI: 10.1074/JBC.273.47.31092

关键词: ThermogenesisBiologyGuanosine monophosphateBrown adipose tissueAdipose tissueCell biologyWhite adipose tissueThermogeninBiochemistryATP synthaseCDNA SubtractionMolecular biology

摘要: 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 inner mitochondrial membrane. This permits respiration uncoupled from ATP synthesis. UCP-1 function inhibited by binding purine nucleotides, with GTP/GDP being more potent than ATP/ADP. We used a cDNA subtraction analysis identify cDNAs rapidly induced exposure. One these encodes rat guanosine monophosphate reductase (GMP-r). was surprising that previous data had suggested this enzyme absent rodents. Rat GMP-r 96% identical human GMP-r, and its mRNA increased 30-fold BAT within 6 h The gene also expressed (but not cold-responsive) muscle kidney, but white fat. speculate physiological marked increase stress may be deplete adipocyte guanine converting them IMP, permitting enhanced function. previously unrecognized regulatory aspect thermogenesis, an essential response cold.

参考文章(28)
W Croteau, J C Davey, V A Galton, D L St Germain, Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. Journal of Clinical Investigation. ,vol. 98, pp. 405- 417 ,(1996) , 10.1172/JCI118806
B.B. Biswas, Richard Abrams, Formation of hypoxanthine from guanine in rat liver extracts Archives of Biochemistry and Biophysics. ,vol. 92, pp. 507- 511 ,(1961) , 10.1016/0003-9861(61)90391-5
Martin Klingenberg, Mechanism and evolution of the uncoupling protein of brown adipose tissue Trends in Biochemical Sciences. ,vol. 15, pp. 108- 112 ,(1990) , 10.1016/0968-0004(90)90194-G
U C Kozak, W Held, D Kreutter, L P Kozak, Adrenergic regulation of the mitochondrial uncoupling protein gene in brown fat tumor cells. Molecular Endocrinology. ,vol. 6, pp. 763- 772 ,(1992) , 10.1210/MEND.6.5.1603085
Martin Bienengraeber, Karim S. Echtay, Martin Klingenberg, H+ Transport by Uncoupling Protein (UCP-1) Is Dependent on a Histidine Pair, Absent in UCP-2 and UCP-3† Biochemistry. ,vol. 37, pp. 3- 8 ,(1998) , 10.1021/BI972463W
Petr Jezek, Keith D. Garlid, David E. Orosz, Martin Modrianský, Stefano Vassanelli, On the Mechanism of Fatty Acid-induced Proton Transport by Mitochondrial Uncoupling Protein Journal of Biological Chemistry. ,vol. 271, pp. 2615- 2620 ,(1996) , 10.1074/JBC.271.5.2615
Chi Shui Lin, Martin Klingenberg, Characteristics of the isolated purine nucleotide binding protein from brown fat mitochondria. Biochemistry. ,vol. 21, pp. 2950- 2956 ,(1982) , 10.1021/BI00541A023
Petr Jezek, Jan Hanus, Craig Semrad, Keith D. Garlid, Photoactivated Azido Fatty Acid Irreversibly Inhibits Anion and Proton Transport through the Mitochondrial Uncoupling Protein Journal of Biological Chemistry. ,vol. 271, pp. 6199- 6205 ,(1996) , 10.1074/JBC.271.11.6199
J. Enrique Silva, Peggy S. Matthews, Full expression of uncoupling protein gene requires the concurrence of norepinephrine and triiodothyronine. Molecular Endocrinology. ,vol. 2, pp. 706- 713 ,(1988) , 10.1210/MEND-2-8-706