Endoplasmic reticulum stress response is involved in the pathogenesis of stress induced gastric lesions in rats.
Stress gastric ulcer is a serious complication, but the mechanism involved is not fully clarified. It is well known that mucosal cell apoptosis plays a crucial role in the pathogenesis of gastric ulceration. Recent studies have shown that endoplasmic reticulum (ER) stress is an important pathway leading to cellular apoptosis. To investigate the role of ER stress in the pathogenesis of stress gastric ulcer, we studied the alteration in the expression of ER stress markers GRP78 (glucose-regulated protein 78) and caspase-12 (an ER stress-specific proapoptotic molecule) and their relations with gastric mucosal apoptosis during development of stress gastric lesions in the water-immersion and restraint stress (WRS) model in rats. Rats developed severe gastric lesions after 6 h of WRS. Typical apoptosis was observed at the edge cells of WRS induced gastric lesions. Western blot analysis showed that GRP78 and activated caspase-12 were over-expressed in the gastric tissues of WRS rats. Immunohistochemical analysis demonstrated that increased GRP78 and caspase-12 were distributed only under the lesions. In addition, dithiothreitol and tunicamycin (ER stress inducers), which increased the expression of GRP78 and activated caspase-12, caused gastric mucosal injury and mucosal cell apoptosis in vitro. These findings suggest that ER stress might be involved in the development of stress gastric ulcer through an apoptotic mechanism.
Lou
Li Xia
LX
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Geng
Bin
B
Yu
Fang
F
Zhang
Jing
J
Pan
Chun Shui
CS
Chen
Li
L
Qi
Yong Fen
YF
Ke
Ya
Y
Wang
Xian
X
Tang
Chao Shu
CS
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D017209:Apoptosis; D053454:Caspase 12; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D064747:Lansoprazole; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D013315:Stress, Psychological / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D053454:Caspase 12; D020169:Caspases; D006360:Heat-Shock Proteins; D064747:Lansoprazole; D018832:Molecular Chaperones; D009853:Omeprazole; D054328:Proton Pump Inhibitors; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat