FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide. J Biol Chem 2011 Mar 11;286(10):8338-8348
Date
01/05/2011Pubmed ID
21196578Pubmed Central ID
PMC3048718DOI
10.1074/jbc.M110.204768Scopus ID
2-s2.0-79953159885 (requires institutional sign-in at Scopus site) 63 CitationsAbstract
For many cell types, including pancreatic β-cells, nitric oxide is a mediator of cell death; paradoxically, nitric oxide can also activate pathways that promote the repair of cellular damage. In this report, a role for FoxO1-dependent transcriptional activation and its regulation by SIRT1 in determining the cellular response to nitric oxide is provided. In response to nitric oxide, FoxO1 translocates from the cytoplasm to the nucleus and stimulates the expression of the DNA repair gene GADD45α, resulting in FoxO1-dependent DNA repair. FoxO1-dependent gene expression appears to be regulated by the NAD(+)-dependent deacetylase SIRT1. In response to SIRT1 inhibitors, the FoxO1-dependent protective actions of nitric oxide (GADD45α expression and DNA repair) are attenuated, and FoxO1 activates a proapoptotic program that includes PUMA (p53-up-regulated mediator of apoptosis) mRNA accumulation and caspase-3 cleavage. These findings support primary roles for FoxO1 and SIRT1 in regulating the cellular responses of β-cells to nitric oxide.
Author List
Hughes KJ, Meares GP, Hansen PA, Corbett JAAuthor
John A. Corbett PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Active Transport, Cell NucleusAnimals
Apoptosis
Apoptosis Regulatory Proteins
Caspase 3
Cell Cycle Proteins
Cell Line
Cell Nucleus
DNA Repair
Endothelium-Dependent Relaxing Factors
Forkhead Box Protein O1
Forkhead Transcription Factors
Insulin-Secreting Cells
Male
Nerve Tissue Proteins
Nitric Oxide
Nuclear Proteins
RNA, Messenger
Rats
Rats, Sprague-Dawley
Sirtuin 1
