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975851 
Journal Article 
Abstract 
Beta cell death by nitric oxide: Is it necrosis, apoptosis or both? 
Corbett, J 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S8-S8 
English 
WOS:000260867900015 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
For many cell types, including pancreatic β-cells, nitric oxide is a mediator of cell death; however, it is paradoxical that for a given cell type nitric oxide can induce both necrosis and apoptosis. In this study, we tested the hypothesis that cell death mediated by nitric oxide shifts from an early necrotic to a late irreversible apoptotic event using insulin secreting pancreatic β-cells. Central to this transition is the ability of β-cells to respond and repair nitric oxide-mediated damage. β-cells have the ability to repair DNA that is damaged following 24 h incubation with IL-1; however, cytokine-induced DNA damage becomes irreversible following 36 h incubation. This irreversible DNA damage following 36 h incubation with IL-1 correlates with the activation of caspase-3 (cleavage and activity). The increase in caspase activity appears to be dependent on the reductions in endogenous nitric oxide production, as nitric oxide is an inhibitor of caspase activity. In contrast, caspase cleavage or activation is not observed under conditions in which β-cells have the ability to repair damaged DNA (24 h incubation with cytokines). Associated with this shift in the form of cell death is a modification in the transcriptional program directed by nitric oxide from protective/repair gene expression to the production of pro-apoptotic gene expression. These findings indicate that β-cell death in response to cytokines shifts from an early necrotic process to apoptosis and that this shift is associated with irreversible DNA damage and caspase 3 activation. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008