Regulation of Cytosolic NADP+-Dependent Isocitrate Dehydrogenase Expression

摘要

The long-range goal of this project is to investigate the mechanisms involved in the regulation of the cytosolic NADP+-depen-dent isocitrate dehydrogenase (IDH1) expression. This dissertation focuses on the central hypothesis that the expression of IDH1 is modulated by regulators of mammary epithelial differentiation and metabolic effectors in bovine mammary epithelium. To test this hypothesis, we examined the mRNA expression of IDH1 in late pregnancy and at various stages of lactation in bovine mammary tissue and demonstrated that IDH1 mRNA levels increased by 2.3-fold after parturition compared to late pregnancy and re-mained constant thereafter. Then, we investigated the effects of extracellular matrix and lactogenic hormones on the expression of IDH1 in cultured BME-UV bovine mammary epithelial cells. We found that the expression of IDH1 mRNA increased in parallel with beta-casein expression during cell differentiation induced by extracellular matrix. Fetal calf serum and insulin repressed whereas prolactin stimulated, the expression of IDH1 mRNA in a dose-dependent fashion. The inhibitory effects of insulin on