Peer-Reviewed Journal Details
Mandatory Fields
McCabe C, Samali A, O'brien T
2006
April
Biochem
beta cell cytoprotective strategies: establishing the relative roles for iNOS and ROS.
Published
WOS: 23 ()
Optional Fields
342
4
1240
1248
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.
10.1016/j.bbrc.2006.02.092
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