GLYCEROL 3-PHOSPHATE DEHYDROGENASE GENE-EXPRESSION IN CULTURED 3T3-L1 ADIPOCYTES - REGULATION BY INSULIN, DEXAMETHASONE AND DIBUTYRYL CAMP AT THE LEVEL OF MESSENGER-RNA ABUNDANCE, TRANSCRIPTION AND MESSENGER-RNA STABILITY
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作者:
BHANDARI, B
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机构:HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,CANC BIOL LAB,BOSTON,MA 02215
BHANDARI, B
SAINI, KS
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机构:HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,CANC BIOL LAB,BOSTON,MA 02215
SAINI, KS
MILLER, RE
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机构:HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,CANC BIOL LAB,BOSTON,MA 02215
MILLER, RE
机构:
[1] HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,CANC BIOL LAB,BOSTON,MA 02215
[2] CASE WESTERN RESERVE UNIV,SCH MED,DEPT MED,CLEVELAND,OH 44106
[3] CASE WESTERN RESERVE UNIV,SCH MED,DEPT BIOCHEM,CLEVELAND,OH 44106
In fully differentiated 3T3-L1 adipocytes, glycerol 3-phosphate dehydrogenase (G3PDH: Sn-glycerol 3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8) is subject to regulation by hormones and dibutyryl cAMP. An increase by insulin (4-fold) and decrease by dexamethasone (by 50%) and dibutyryl cAMP (by 70%) was observed for G3PDH mRNA abundance as analyzed by Northern blot hybridization. In addition, incubation of adipocytes with dibutyryl cAMP resulted in 3-fold increase in G3PDH gene transcription as measured by nuclear transcript elongation assay. The effects of these modulators on the control of G3PDH mRNA stability were also investigated. The G3PDH mRNA has a half-life of about 125 min. Dibutyryl cAMP caused an increase in G3PDH mRNA degradation by > 2-fold (t1/2 = 55 min) whereas insulin had an opposite effect (t1/2 = 240 min) and dexamethasone was without any effect on G3PDH mRNA stability. Taken together, our results directly demonstrate that in fully differentiated 3T3-L1 adipocytes the regulation of G3PDH gene expression by dibutyryl cAMP and insulin is exerted by alterations in transcription as well as mRNA stability.