Inhibitory roles of protein kinase B and peroxisome proliferator-activated receptor gamma coactivator on hepatic HMG-CoA reductase promoter activity — Oak Academic Publishing
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Inhibitory roles of protein kinase B and peroxisome proliferator-activated receptor gamma coactivator on hepatic HMG-CoA reductase promoter activity
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, USA
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Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, USA
1 Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, USA
2 Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, USA
Since we had previously demonstrated that siRNAs to tristetraprolin (TTP) markedly inhibited insulin stimulation of hepatic HMG-CoA reductase (HMGR) transcription, we investigated the effects of transfect ing rat liver with TTP constructs. We found that transfecting diabetic rats with TTP did not increase HMGR transcription but rather led to modest inhibition. We then investigated whether co-transfection with pro tein kinase B, hepatic form (AKT2), might lead to pho sphorylation and result in activation of HMGR transcription. We found that this treatment resulted in near complete inhibition of transcription. Transfection with peroxisome proliferator-activated receptor g coactivator (PGC-1 a ) also inhibited HMGR transcription. These results show that although TTP is needed for activation of HMGR transcription, it cannot by itself activate this process. AKT2 and PGC-1 a , which mediate the activation of gluconeogenic genes by insulin, exert the opposite effect on HMGR.
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