Peer-Reviewed Journal Details
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McCabe, C,Samali, A,O'Brien, T
2006
April
Biochemical And Biophysical Research Communications
beta cell cytoprotective strategies: Establishing the relative roles for iNOS and ROS
Published
()
Optional Fields
beta cells cytokines inducible nitric oxide synthase. reactive oxygen species antioxidants I kappa B alpha gene transfer cytoprotection adenovirus MANGANESE SUPEROXIDE-DISMUTASE NITRIC-OXIDE SYNTHASE FACTOR-KAPPA-B ADENOVIRUS-MEDIATED EXPRESSION INSULIN-PRODUCING CELLS OXYGEN-FREE RADICALS GENE-TRANSFER ANTIOXIDANT ENZYMES HUMAN ISLETS RINM5F CELLS
342
1240
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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-kappa B inhibition, using a degradation-resistant mutant of I kappa B alpha. NF-kappa B 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 NOS, 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. (c) 2006 Elsevier Inc. All rights reserved.
DOI 10.1016/j.bbrc.2006.02.092
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