AMP-activated protein kinase attenuates nitric oxide-induced beta-cell death. J Biol Chem 2010 Jan 29;285(5):3191-200
Date
11/26/2009Pubmed ID
19933272Pubmed Central ID
PMC2823419DOI
10.1074/jbc.M109.047365Scopus ID
2-s2.0-77449100323 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
During the initial autoimmune response in type 1 diabetes, islets are exposed to a damaging mix of pro-inflammatory molecules that stimulate the production of nitric oxide by beta-cells. Nitric oxide causes extensive but reversible cellular damage. In response to nitric oxide, the cell activates pathways for functional recovery and adaptation as well as pathways that direct beta-cell death. The molecular events that dictate cellular fate following nitric oxide-induced damage are currently unknown. In this study, we provide evidence that AMPK plays a primary role controlling the response of beta-cells to nitric oxide-induced damage. AMPK is transiently activated by nitric oxide in insulinoma cells and rat islets following IL-1 treatment or by the exogenous addition of nitric oxide. Active AMPK promotes the functional recovery of beta-cell oxidative metabolism and abrogates the induction of pathways that mediate cell death such as caspase-3 activation following exposure to nitric oxide. Overall, these data show that nitric oxide activates AMPK and that active AMPK suppresses apoptotic signaling allowing the beta-cell to recover from nitric oxide-mediated cellular stress.
Author List
Meares GP, Hughes KJ, Jaimes KF, Salvatori AS, Rhodes CJ, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AMP-Activated Protein KinasesAconitate Hydratase
Animals
Caspase 3
Cell Death
Cell Lineage
Comet Assay
Insulin-Secreting Cells
Insulinoma
Interleukin-1
Male
Nitric Oxide
Nitrites
Rats
Rats, Sprague-Dawley
