Melanocortin 1 Receptor Agonist Protects Podocytes Through Catalase and RhoA Activation.

Melanocortin 1 Receptor Agonist Protects Podocytes Through Catalase and RhoA Activation. Am J Physiol Renal Physiol. 2016 Feb 17;:ajprenal.00231.2015 Authors: Elvin J, Buvall L, Lindskog Jonsson A, Granqvist A, Lassén E, Bergwall L, Nyström J, Haraldsson B Abstract Drugs containing adrenocorticotropic hormone (ACTH) have been used as therapy for patients with nephrotic syndrome. We have previously shown that ACTH and a selective agonist for the melanocortin 1 receptor (MC1R) exert beneficial actions in experimental membranous nephropathy with reduced proteinuria, reduced oxidative stress, improved glomerular morphology and function. Our hypothesis is that MC1R activation in podocytes elicits beneficial effects by promoting stress fibers and maintaining podocyte viability. To test the hypothesis, we cultured podocytes and used highly specific agonists for the MC1R. The podocytes were subjected to the nephrotic-inducing agent puromycin aminonucleoside and downstream effects of MC1R activation on podocyte survival; antioxidant defense and cytoskeleton dynamics were studied. To increase the response and enhance the intracellular signals, podocytes were transduced to overexpress MC1R. We show that puromycin promotes MC1R expression in podocytes and that activation of the MC1R promotes an increase of catalase activity and reduces oxidative stress, which results in dephosphorylation of p190RhoGAP and formation of stress fibers through Rho...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research