TY - JOUR
T1 - Ammonia aggravates stress-induced gastric mucosal oxidative injury through the cancellation of cytoprotective heat shock protein 70
AU - Nagahashi, Shoichi
AU - Suzuki, Hidekazu
AU - Miyazawa, Masaharu
AU - Nagata, Hiroshi
AU - Suzuki, Masayuki
AU - Miura, Soichiro
AU - Ishii, Hiromasa
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research C from the Ministry of Education, Science, and Culture of Japan (13670555), by a Keio University Medical School Faculty and Alumni Grant (94-0009), and by a grant from the Uehara Memorial Life Science Funds. The preliminary report of this study was presented at Digestive Disease Week 2000, held in San Diego, CA, USA in May 2000. Part of this study was also presented at the Symposium on Free Radicals in Digestive Diseases at the Tenth Biennial Meeting of the Society of Free Radical Research International, held in Kyoto, Japan in October 2000.
PY - 2002/10/15
Y1 - 2002/10/15
N2 - The relationship between Helicobacter pylori colonization and the formation of stress-induced gastric mucosal injury remains unknown. Since ammonia (NH3) is known as one of the injurious factors in H. pylori-colonized gastric mucosa, the present study is designed to investigate the level of stress-induced gastric mucosal oxidative injury with or without intragastric NH3 overloading. To apply emotional stress, the communication box paradigm was used in the mouse model. Mice (C57BL/6, male) were pretreated with distilled water (responder-H2O) or 0.01% NH3 (responder-NH3) through a gastric tube once a day for a week. Emotional stress was then applied to the responder mice for 3 h per day for 3 d by watching and hearing the behavior of the sender mice subjected to electric shocks to the feet (2 mA, 10 s, 50 s interval). After the communication box protocol, the tissue MPO activity, the contents of TBA-reactive substances (TBARS), and the level of gastric mucosal HSP70 were examined. Responder-NH3 mice developed more severe gastric lesions than the responder-H2O subjects. MPO activity and TBARS contents were enhanced significantly in the responder-NH3 group compared with the responder-H2O subjects. Although the contents of HSP70 in the gastric mucosa increased in the responder-H2O group compared with the control-H2O animals, they were significantly attenuated in the responder-NH3 mice. Excess intragastric NH3 was able to enhance the formation of emotional stress-induced gastric mucosal lesions. This injury may be associated with the enhanced production of oxygen free radicals from accumulated neutrophils under the NH3-mediated cancellation of gastric mucosal cytoprotective HSP70.
AB - The relationship between Helicobacter pylori colonization and the formation of stress-induced gastric mucosal injury remains unknown. Since ammonia (NH3) is known as one of the injurious factors in H. pylori-colonized gastric mucosa, the present study is designed to investigate the level of stress-induced gastric mucosal oxidative injury with or without intragastric NH3 overloading. To apply emotional stress, the communication box paradigm was used in the mouse model. Mice (C57BL/6, male) were pretreated with distilled water (responder-H2O) or 0.01% NH3 (responder-NH3) through a gastric tube once a day for a week. Emotional stress was then applied to the responder mice for 3 h per day for 3 d by watching and hearing the behavior of the sender mice subjected to electric shocks to the feet (2 mA, 10 s, 50 s interval). After the communication box protocol, the tissue MPO activity, the contents of TBA-reactive substances (TBARS), and the level of gastric mucosal HSP70 were examined. Responder-NH3 mice developed more severe gastric lesions than the responder-H2O subjects. MPO activity and TBARS contents were enhanced significantly in the responder-NH3 group compared with the responder-H2O subjects. Although the contents of HSP70 in the gastric mucosa increased in the responder-H2O group compared with the control-H2O animals, they were significantly attenuated in the responder-NH3 mice. Excess intragastric NH3 was able to enhance the formation of emotional stress-induced gastric mucosal lesions. This injury may be associated with the enhanced production of oxygen free radicals from accumulated neutrophils under the NH3-mediated cancellation of gastric mucosal cytoprotective HSP70.
KW - Free radicals
KW - Heat shock protein 70
KW - Helicobacter pylori
KW - Lipid peroxide
KW - Myeloperoxidase
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U2 - 10.1016/S0891-5849(02)00998-X
DO - 10.1016/S0891-5849(02)00998-X
M3 - Article
C2 - 12374618
AN - SCOPUS:0037108205
VL - 33
SP - 1073
EP - 1081
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 8
ER -