title: p38MAPK suppresses chronic pancreatitis by regulating HSP27 and BAD expression.
abstract: 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-α plus actinomycin D. In conclusion, p38MAPK suppresses chronic pancreatitis by upregulating HSP27 expression and downregulating BAD expression.
authors.affiliation: Department of Biochemistry, Kinki University, Faculty of Medicine, Osaka 589-8511, Japan.
authors.forename: Ah-Mee
authors.initials: AM
authors.lastname: Park
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Satoru
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Masaki
authors.initials: M
authors.lastname: Tabuchi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Munakata
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D055551:HSP27 Heat-Shock Proteins; D007093:Imidazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051025:bcl-Associated Death Protein; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580