Oxidant driven signaling pathways during diabetes: role of Rac1 and modulation of protein kinase activity in mouse urinary bladder

Biochimie
Deepali Pitre Poladia, J A Bauer

Abstract

Urinary bladder dysfunction is a complication in diabetes but the mechanisms involved are undefined. Here, we investigated roles of oxidative stress and oxidant driven signaling pathways in a murine model of diabetes, with an emphasis on urothelial vs. smooth muscle regional changes. Mice were dosed with streptozotocin (150 mg/kg) or vehicle and studied at 5 weeks. Functional changes were assessed by in vitro cystometry. Immunohistochemical methods and automated digital imaging was used for morphometric and histochemical analysis of bladder tissue regions. We detected significant increases in protein 3-nitrotyrosine in both urothelium and smooth muscle regions during diabetes, demonstrating an increased prevalence of reactive nitrogen species. In light of nitric oxide synthase (NOS) isoforms as potential contributors to increased protein nitration, all three NOS isoforms were studied; region specific increases in NOS1 (urothelium and smooth muscle), NOS2 (urothelium only) but no alterations in NOS3 isoform were detected during diabetes. In contrast, p21-Rac1 (coordinating protein of NADPH oxidase) was significantly increased only in smooth muscle (diabetic vs. controls). We also investigated phosphorylation of ERK, JNK, p38 and...Continue Reading

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Citations

Jul 16, 2005·International Urogynecology Journal and Pelvic Floor Dysfunction·Diaa E E RizkIjaz Ahmed
Mar 14, 2008·Molecular & Cellular Proteomics : MCP·Elizabeth YohannesMark R Chance
Jun 11, 2005·The Journal of Urology·Anita S MannikarottuSamuel Chacko
Oct 8, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ketrija TouwB Paul Herring
Apr 12, 2008·The American Journal of Pathology·Maryla KrajewskaStan Krajewski
Aug 19, 2006·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Zhenlin JuRonald B Walter
Nov 11, 2014·Basic & Clinical Pharmacology & Toxicology·Atiye Sinem EvcimMukaddes Gumustekin

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