| RRC ID |
43059
|
| Author |
Tan A, Nakamura H, Kondo N, Tanito M, Kwon YW, Ahsan MK, Matsui H, Narita M, Yodoi J.
|
| Title |
Thioredoxin-1 attenuates indomethacin-induced gastric mucosal injury in mice.
|
| Journal |
Free Radic Res
|
| Abstract |
Indomethacin is one of non-steroidal anti-inflammatory drugs that are commonly used clinically and often cause gastric mucosal injury as a side effect. Generation of reactive oxygen species (ROS) and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric mucosal injury. Thioredoxin-1 (Trx-1) is a small redox-active protein with anti-oxidative activity and redox-regulating functions. The aim of this study was to investigate the protective effect of Trx-1 against indomethacin-induced gastric mucosal injury. Trx-1 transgenic mice displayed less gastric mucosal damage than wild type (WT) C57BL/6 mice after intraperitoneal administration of indomethacin. Administration of recombinant human Trx-1 (rhTrx-1) or transfection of the Trx-1 gene reduced indomethacin-induced cytotoxicity in rat gastric epithelial RGM-1 cells. Pretreatment with rhTrx-1 suppressed indomethacininduced ROS production and downregulation of phosphorylated Akt in RGM-1 cells. Survivin, a member of inhibitors of apoptosis proteins family, was downregulated by indomethacin, which was suppressed in Trx-1 transgenic mice or by administration of rhTrx-1 in RGM-1 cells. Trx-1 inhibits indomethacin-induced apoptotic signaling and gastric ulcer formation, suggesting that it may have a preventive and therapeutic potential against indomethacin-induced gastric injury.
|
| Volume |
41(8)
|
| Pages |
861-9
|
| Published |
2007-8-1
|
| DOI |
10.1080/10715760701199618
|
| PII |
780572715
|
| PMID |
17654042
|
| MeSH |
Animals
Anti-Inflammatory Agents, Non-Steroidal / antagonists & inhibitors*
Anti-Inflammatory Agents, Non-Steroidal / toxicity
Apoptosis / drug effects
Apoptosis / genetics
Cell Line
Gastric Mucosa / drug effects*
Gastric Mucosa / metabolism
Indomethacin / antagonists & inhibitors*
Indomethacin / toxicity
Mice
Mice, Transgenic
Rats
Reactive Oxygen Species / antagonists & inhibitors
Reactive Oxygen Species / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / pharmacology
Thioredoxins / genetics
Thioredoxins / metabolism
Thioredoxins / pharmacology*
|
| IF |
2.839
|
| Times Cited |
25
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
RGM1(RCB0876) |
