p38MAPK suppresses chronic pancreatitis by regulating HSP27 and BAD expression

详细信息	查看全文 | 推荐本文 |

• 作者：Ah-Mee Park^a ; Masatoshi Kudo^b ; Satoru Hagiwara^b ; Masaki Tabuchi^c ; Tomohiro Watanabe^d ; Hiroshi Munakata^a ; Toshiharu Sakurai^b ; ^{sakurai@med.kindai.ac.jp}
• 关键词：4-HNE ; 4-hydroxynonenal ; ActD ; actinomycin D ; BAD ; Bcl-2 antagonist of cell death ; DEN ; diethylnitrosamine ; H&E ; hematoxylin and eosin ; HSP27 ; heat shock protein 27 ; IL ; interleukin ; JNK ; c-Jun N-terminal kinase ; MAPK ; mitogen-activated protein kinase ; MP
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：1-15 June, 2012
• 卷：52
• 期：11-12
• 页码：2284-2291
• 文件大小：828 K

摘要

Mitogen-activated protein kinases (MAPKs) are ubiquitous proteins that function in both normal and stress-related pathophysiological states of the cell. This study aimed to analyze the importance of p38MAPK in pancreatic injury using WBN/Kob rats with spontaneous chronic pancreatitis. Male WBN/Kob rats were injected with the p38MAPK inhibitor SB203580, starting at the age of 4 weeks, and sacrificed 6 weeks later. Compared with vehicle-treated rats, p38 inhibitor-treated rats exhibited a significant increase in pancreatic cell death and inflammation as assessed by histologic examination and myeloperoxidase activity, respectively. p38 inhibition decreased the expression of heat shock protein 27 (HSP27), an antioxidant protein, and enhanced accumulation of reactive oxygen species (ROS). In addition, the proapoptotic protein BAD was increased in the pancreas of rats treated with p38 inhibitor. In a pancreatic cell line (PANC-1), HSP27 knockdown augmented reactive oxygen species accumulation and cell death induced by tumor necrosis factor-伪 plus actinomycin D. In conclusion, p38MAPK suppresses chronic pancreatitis by upregulating HSP27 expression and downregulating BAD expression.