Regulation of soluble epoxide hydrolase (sEH) in mice with diabetes: high glucose suppresses sEH expression.
Soluble epoxide hydrolase (sEH) is a xenobiotic-metabolizing enzyme that metabolizes epoxides to produce vicinal diols. Diabetes is a common pathological condition which effects drug metabolism. This study, investigates changes in the levels of sEH in mice with diabetes induced by streptozotocin (STZ). Diabetes reduced the amount of sEH protein in the liver and insulin restored the level of protein. The kidneys are a target of diabetes. Diabetes significantly decreased levels of sEH protein and also mRNA. The distribution of sEH in the kidney was studied with immunostaining. There was distinct staining in the proximal tubules but not in the glomerulus or other regions. Diabetes is characterized by high glucose concentrations that lead to increased production of reactive oxygen species (ROS). High glucose suppressed sEH mRNA and protein expression in Hep3B cells. NADPH oxidase is the main source of ROS generation in high glucose condition. The NADPH oxidase inhibitor, diphenyleneiodonium chloride (DPIC), inhibited decrease in sEH expression at high glucose and hydrogen peroxide suppressed sEH expression. These findings indicate that diabetes reduces sEH expression by inducing ROS and may have important effects on the metabolism of xenobiotics and endogenous substrates of sEH.
Oguro
Ami
A
Nanobiotechnology Research Center and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Japan.
Fujita
Natsuko
N
Imaoka
Susumu
S
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000096:biosynthesis / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009861:Onium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D009861:Onium Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; D003577:Cytochrome P-450 Enzyme System; D019255:NADPH Oxidases; D004851:Epoxide Hydrolases; D005947:Glucose