| RRC ID |
43814
|
| 著者 |
Park AM, Kudo M, Hagiwara S, Tabuchi M, Watanabe T, Munakata H, Sakurai T.
|
| タイトル |
p38MAPK suppresses chronic pancreatitis by regulating HSP27 and BAD expression.
|
| ジャーナル |
Free Radic Biol Med
|
| 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.
|
| 巻・号 |
52(11-12)
|
| ページ |
2284-91
|
| 公開日 |
2012-6-1
|
| DOI |
10.1016/j.freeradbiomed.2012.03.010
|
| PII |
S0891-5849(12)00181-5
|
| PMID |
22549003
|
| MeSH |
Animals
Cell Line, Tumor
Disease Models, Animal
Gene Expression Regulation
HSP27 Heat-Shock Proteins / genetics
HSP27 Heat-Shock Proteins / metabolism*
Humans
Imidazoles / administration & dosage
Male
Pancreatitis, Chronic / chemically induced
Pancreatitis, Chronic / genetics
Pancreatitis, Chronic / metabolism*
Pyridines / administration & dosage
RNA, Small Interfering / genetics
Rats
Rats, Inbred Strains
Reactive Oxygen Species / metabolism
bcl-Associated Death Protein / genetics
bcl-Associated Death Protein / metabolism*
p38 Mitogen-Activated Protein Kinases* / antagonists & inhibitors
|
| IF |
6.17
|
| 引用数 |
5
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
