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Nitric oxide induces ataxia telangiectasia mutated (ATM) protein-dependent γH2AX protein formation in pancreatic β cells. J Biol Chem 2014 Apr 18;289(16):11454-64

Date

03/13/2014

Pubmed ID

24610783

Pubmed Central ID

PMC4036281

DOI

10.1074/jbc.M113.531228

Scopus ID

2-s2.0-84898944668   19 Citations

Abstract

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 JA

Authors

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin
Vera Tarakanova PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
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
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a