Nitric oxide induces ataxia telangiectasia mutated (ATM) protein-dependent γH2AX protein formation in pancreatic β cells. J Biol Chem 2014 Apr 18;289(16):11454-11464
Date
03/13/2014Pubmed ID
24610783Pubmed Central ID
PMC4036281DOI
10.1074/jbc.M113.531228Scopus ID
2-s2.0-84898944668 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
In this study, the effects of cytokines on the activation of the DNA double strand break repair factors histone H2AX (H2AX) and ataxia telangiectasia mutated (ATM) were examined in pancreatic β cells. We show that cytokines stimulate H2AX phosphorylation (γH2AX formation) in rat islets and insulinoma cells in a nitric oxide- and ATM-dependent manner. In contrast to the well documented role of ATM in DNA repair, ATM does not appear to participate in the repair of nitric oxide-induced DNA damage. Instead, nitric oxide-induced γH2AX formation correlates temporally with the onset of irreversible DNA damage and the induction of apoptosis. Furthermore, inhibition of ATM attenuates cytokine-induced caspase activation. These findings show that the formation of DNA double strand breaks correlates with ATM activation, irreversible DNA damage, and ATM-dependent induction of apoptosis in cytokine-treated β cells.
Author List
Oleson BJ, Broniowska KA, Schreiber KH, Tarakanova VL, Corbett JAAuthors
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinVera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Ataxia Telangiectasia Mutated Proteins
Caspases
Cell Line, Tumor
Cytokines
DNA Breaks, Double-Stranded
Enzyme Activation
Histones
Insulin-Secreting Cells
Male
Nitric Oxide
Phosphoproteins
Phosphorylation
Rats
Rats, Sprague-Dawley
