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Oxidative stress induces apoptosis via calpain- and caspase-3-mediated cleavage of ATM in pancreatic acinar cells

Authors
 Soon Ok Cho  ;  Joo Weon Lim  ;  Hyeyoung Kim 
Citation
 FREE RADICAL RESEARCH, Vol.54(11~12) : 799-809, 2020-12 
Journal Title
FREE RADICAL RESEARCH
ISSN
 1071-5762 
Issue Date
2020-12
MeSH
Acinar Cells / metabolism ; Acinar Cells / pathology ; Animals ; Apoptosis / physiology ; Ataxia Telangiectasia / metabolism* ; Ataxia Telangiectasia Mutated Proteins / metabolism* ; Calpain / metabolism* ; Caspase 3 / metabolism* ; Cell Line, Tumor ; Humans ; Oxidative Stress / physiology ; Pancreatic Neoplasms / metabolism* ; Pancreatic Neoplasms / pathology ; Rats
Keywords
Ataxia telangiectasia mutated ; calpain ; caspase-3 ; glucose ; glucose oxidase ; pancreatic acinar cells
Abstract
Oxidative stress-induced DNA cleavage and apoptosis in pancreatic acinar cells has been implicated in the pathogenesis of acute pancreatitis. Thus, an efficient DNA repair process is key to prevention of apoptotic pancreatic acinar cell death. Ataxia telangiectasia mutated (ATM), a sensor of DNA breaks, functions by recruiting DNA repair proteins to initiate the DNA repair process. In the present study, we investigated whether H2O2 produced by the action of glucose oxidase on alpha-D-glucose (G/GO) induces apoptosis in pancreatic acinar AR42J cells through an alteration of the level of ATM. As a result, G/GO induced apoptosis by promoting a loss of cell viability, increase in Bax, decrease in Bcl-2, cleavage of poly (ADP-ribose) polymerase (PARP) and fragmentation of DNA. In addition, ATM cleavage along with elevated levels of calpain and caspase-3 activity was induced by G/GO. By using ATM siRNA, we demonstrated that reduction in ATM levels enhanced G/GO-induced apoptosis. Moreover, inhibition of calpain activity by calpeptin or calpastatin, or by inhibition of caspase-3 with z-DEVD, suppressed G/GO-induced apoptosis and ATM cleavage. Collectively, these findings suggest that proteolysis of ATM is the underlying mechanism of apoptosis of pancreatic acinar cells caused by exposure to oxidative stress.
Full Text
https://www.tandfonline.com/doi/abs/10.1080/10715762.2019.1655145?journalCode=ifra20
DOI
10.1080/10715762.2019.1655145
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189912
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