Suppressing Cyclooxygenase-2 Prevents nonalcoholic and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

Cyclooxygenase-2 (COX-2) can exert pro-inflammatory effects in nonalcoholic steatohepatitis (NASH). The aim of this study was to determine if the inhibition of COX-2 attenuates hepatocyte apoptosis in steatohepatitis and to examine the underlying molecular mechanism. Male wild type C57BL6/J mice and...

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Published in:Biochemical and biophysical research communications 2016, Vol.469 (22), p.1034-1040
Main Authors: Wu, Jialing, Chong Chen, Xi Hu, Xianbin Cai, Yinghong Guan, Hui Hu, Qinjia Wang, Xiaofeng Chen, Bozhi Cai, Xubin Jing
Format: Article
Language:English
Subjects:
Akt
alanine transaminase
Apoptosis
blood serum
Celecoxib
choline
COX-2
diet
fatty liver
hepatocytes
histology
liver
males
methionine
mice
Nonalcoholic steatohepatitis
p53
prostaglandin synthase
signal transduction
triacylglycerols
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Summary:Cyclooxygenase-2 (COX-2) can exert pro-inflammatory effects in nonalcoholic steatohepatitis (NASH). The aim of this study was to determine if the inhibition of COX-2 attenuates hepatocyte apoptosis in steatohepatitis and to examine the underlying molecular mechanism. Male wild type C57BL6/J mice and COX-2 knock out (COX-2−/−) mice were fed a methionine choline deficient (MCD) diet for 3 weeks. The wild type mice were also treated with celecoxib or a combination of celecoxib and a Akt specific inhibitor, miltefosine (MTF). After that, liver histology, serum alanine aminotransferase (ALT) levels, hepatic triglyceride (TG) levels, hepatocyte apoptosis, phosphorylated Akt (Ser473, pAkt) and p53 protein levels in mice livers were assessed. Celecoxib attenuated the severity of liver steatohepatitis and reduced the number of apoptotic cells, accompanied by increasing the activity of Akt and decreasing expression of p53. On the contrary, MTF can abrogate the effects of celecoxib on anti-apoptosis and anti-steatohepatitis. Moreover, the effects on the COX-2−/− mice that were fed the MCD diet were similar to that for celecoxib. The findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH.
ISSN:0006-291X
1090-2104