myo-Inositol Oxygenase Overexpression Accentuates Generation of Reactive Oxygen Species and Exacerbates Cellular Injury following High Glucose Ambience: A NEW MECHANISM RELEVANT TO THE PATHOGENESIS OF DIABETIC NEPHROPATHY.

The Journal of Biological Chemistry
L SunY S Kanwar

Abstract

Diabetic nephropathy (DN) is characterized by perturbations in metabolic/cellular signaling pathways with generation of reactive oxygen species (ROS). The ROS are regarded as a common denominator of various pathways, and they inflict injury on renal glomerular cells. Recent studies indicate that tubular pathobiology also plays a role in the progression of DN. However, the mechanism(s) for how high (25 mm) glucose (HG) ambience induces tubular damage remains enigmatic. myo-Inositol oxygenase (MIOX) is a tubular enzyme that catabolizes myo-inositol to d-glucuronate via the glucuronate-xylulose (G-X) pathway. In this study, we demonstrated that G-X pathway enzymes are expressed in the kidney, and MIOX expression/bioactivity was up-regulated under HG ambience in LLC-PK1 cells, a tubular cell line. We further investigated whether MIOX overexpression leads to accentuation of tubulo-interstitial injury, as gauged by some of the parameters relevant to the progression of DN. Under HG ambience, MIOX overexpression accentuated redox imbalance, perturbed NAD(+)/NADH ratios, increased ROS generation, depleted reduced glutathione, reduced GSH/GSSG ratio, and enhanced adaptive changes in the profile of the antioxidant defense system. These ch...Continue Reading

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Citations

Nov 30, 2016·Journal of the American Society of Nephrology : JASN·Rajesh K DuttaYashpal S Kanwar
Dec 1, 2017·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Cuma MertogluTaha Abdulkadir Coban
Dec 13, 2018·American Journal of Physiology. Renal Physiology·Tatsuya TominagaYashpal S Kanwar
Sep 22, 2017·American Journal of Physiology. Renal Physiology·Isha SharmaYashpal S Kanwar
Dec 26, 2018·Journal of Medical Biochemistry·Cuma MertogluMehmet Gungor
Sep 21, 2017·Journal of Diabetes Research·Yu YangJun-Kai Duan
Jan 13, 2018·International Journal of Molecular Medicine·Jinying WeiHuijun Duan

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