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Uncontrolled diabetes results in enhanced expression of cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A. Because of the simultaneous and confounding metabolic and hormonal changes that occur in vivo as a consequence of diabetes, primary cultured rat hepatocytes provide an excellent model system for examination of the effects of insulin on P-450(More)
BACKGROUND Diabetes is a major threat to public health in the United States and worldwide. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. OBJECTIVE We assessed the epidemiologic literature for evidence of associations between persistent organic pollutants (POPs)(More)
Oxidative damage to DNA is thought to play a significant role in mutagenesis, aging, and cancer. Sensitivity to oxidative DNA damage and DNA repair efficiency were examined using a series of human breast epithelial cell lines-MCF-10A, MCF-10AT, and MCF-10ATG3B-with progressively elevated Ras protein. Breast epithelial cells were treated with H2O2, in the(More)
The distribution of glutathione (GSH) and glutathione S-transferases (GSTs) in the adult rat brain is cell-type specific, but their cellular distribution in the developing central nervous system is unknown. In the present study, GSH distribution in the mouse nervous system was visualized by mercury orange histochemistry and class-specific GSTs were(More)
Cytochrome P450 2E1 (CYP2E1) and 2B (CYP2B) mRNA and protein expression was examined in primary cultured rat hepatocytes under basal cell culture conditions and in response to three prototypic CYP2E1 inducers, i.e. ethanol, acetone, and pyrazine. Xenobiotic treatment for 24 hr, initiated after hepatocytes had been maintained in culture for 72 hr, resulted(More)
Glutathione and its related enzymes play a major role in the detoxification of toxic chemicals. In rat brain the pattern of distribution of reduced glutathione exhibits cellular heterogeneity, suggesting also the possibility of cellular differences in glutathione conjugating capacity. To understand the potential role of GSH in detoxification of(More)
Discovered less than a decade ago, micro-RNAs (miRNAs) have emerged as important regulators of gene expression in mammals. They consist of short nucleic acids, on average approximately 22 nucleotides in length. The miRNAs exert their effect by binding directly to target messenger RNAs (mRNAs) and inhibiting mRNA stability and translation. Each miRNA can(More)
The distribution of several cytochrome P-450 (P-450) isoenzymes between proximal tubular (PT) and distal tubular (DT) cells of the rat kidney was determined. Western blot analysis of microsomes prepared from liver and kidney cortical homogenates revealed that CYP2E1 protein was expressed in rat kidney microsomes at approximately 10% of hepatic levels.(More)
Diabetes is characterized by elevated levels of ketone bodies acetoacetate (AA) and 3-hydroxybutyrate (3HB). High levels of ketone bodies have been implicated in generation of cellular oxidative stress. Ketone body activation of cellular signaling pathways associated with oxidative stress, however, has not been established. Thus, ketone body effects on(More)
Diabetes is a major cause of morbidity and mortality, and complications resulting from diabetes have been attributed in part to increased oxidative stress. Glutathione S-transferases (GSTs) constitute a major protective mechanism against oxidative stress. Studies of the expression and activity of GSTs during diabetes are inconclusive, with both increased(More)