beta cell cytoprotective strategies: establishing the relative roles for iNOS and ROS

Biochemical and Biophysical Research Communications
Cillian McCabeTimothy O'Brien

Abstract

Cytokine-induced beta cell destruction may be mediated by the generation of nitric oxide and/or reactive oxygen species. The relative importance of NO and ROS in cytokine-induced beta cell pathophysiology remains unclear. This investigation evaluates and contrasts the cytoprotective potential of antioxidant gene transfer, versus NF-kappaB inhibition, using a degradation-resistant mutant of IkappaBalpha. NF-kappaB inhibition conferred significant protection against cytokine-induced damage whereas antioxidant overexpression failed to provide protection. Conferred cytoprotection was associated with a suppression of iNOS activation and nitrite accumulation. Our data implicates iNOS, as opposed to ROS, as the pivotal player in cytokine-induced beta cell damage. From a therapeutic standpoint, strategies aimed at targeting the activation of iNOS may harbor therapeutic potential in preserving beta cell survival in the face of proinflammatory cytokine exposure.

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Citations

Jul 24, 2010·Pflügers Archiv : European journal of physiology·Gisela DrewsMartina Düfer
Jun 4, 2008·Folia Histochemica Et Cytobiologica·Nurullah Keklikoglu
Jun 21, 2011·International Journal of Molecular Sciences·Haider RazaNarayan G Avadhani
Dec 18, 2007·Journal of Cellular and Molecular Medicine·C HolohanA Samali
Apr 23, 2016·Diabetes/metabolism Research and Reviews·Gloria Baena-NietoAlfonso M Lechuga-Sancho
Apr 5, 2007·Biochemical and Biophysical Research Communications·Cillian McCabe, Timothy O'Brien
Oct 5, 2010·Diabetes/metabolism Research and Reviews·A Roeske-NielsenK Buschard
Oct 22, 2009·American Journal of Physiology. Endocrinology and Metabolism·Grégory LacrazBernard Portha
Jan 26, 2008·Molecular Pharmaceutics·Feng Li, Ram I Mahato

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