β cell cytoprotective strategies: Establishing the relative roles for iNOS and ROS

• Published in: Biochemical and biophysical research communications 2006-04, Vol.342 (4), p.1240-1248
• Main Authors: McCabe, Cillian, Samali, Afshin, O’Brien, Timothy
• Format: Article
• Language: English
• Subjects: Adenovirus; Animals; Antioxidants; Cell Line; Cell Survival - drug effects; Cytokines; Cytokines - administration & dosage; Cytoprotection; Cytoprotection - physiology; Gene transfer; I-kappa B Proteins - metabolism; Inducible nitric oxide synthase; Insulin-Secreting Cells - metabolism; IκBα; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; β cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.02.092

Cytokine-induced β 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 β cell pathophysiology remains unclear. This investigation evaluates and contrasts the cytoprotective potential of antioxidant gene transfer, versus NF-κB inhibition, using a degradation-resistant mutant of IκBα. NF-κB 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 β 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.