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

Authors
Journal
Biochemical and Biophysical Research Communications
0006-291X
Publisher
Elsevier
Publication Date
Volume
342
Issue
4
Identifiers
DOI: 10.1016/j.bbrc.2006.02.092
Keywords
  • β Cells
  • Cytokines
  • Inducible Nitric Oxide Synthase
  • Reactive Oxygen Species
  • Antioxidants
  • IκBα
  • Gene Transfer
  • Cytoprotection
  • Adenovirus
Disciplines
  • Biology
  • Medicine

Abstract

Abstract 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.

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