Ammonia aggravates stress-induced gastric mucosal oxidative injury through the cancellation of cytoprotective heat shock protein 70.
The relationship between Helicobacter pylori colonization and the formation of stress-induced gastric mucosal injury remains unknown. Since ammonia (NH(3)) 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 NH(3) 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-H(2)O) or 0.01% NH(3) (responder-NH(3)) 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-NH(3) mice developed more severe gastric lesions than the responder-H(2)O subjects. MPO activity and TBARS contents were enhanced significantly in the responder-NH(3) group compared with the responder-H(2)O subjects. Although the contents of HSP70 in the gastric mucosa increased in the responder-H(2)O group compared with the control-H(2)O animals, they were significantly attenuated in the responder-NH(3) mice. Excess intragastric NH(3) 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 NH(3)-mediated cancellation of gastric mucosal cytoprotective HSP70.
Nagahashi
Shoichi
S
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
Hidekazu
H
Miyazawa
Masaharu
M
Nagata
Hiroshi
H
Suzuki
Masayuki
M
Miura
Soichiro
S
Ishii
Hiromasa
H
D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D004597:Electroshock; D004644:Emotions; D005609:Free Radicals / Q000378:metabolism; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000032:analysis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D016481:Helicobacter Infections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications*; D013482:Superoxide Dismutase / Q000032:analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014867:Water / Q000494:pharmacology
D005609:Free Radicals; D018840:HSP70 Heat-Shock Proteins; D017392:Thiobarbituric Acid Reactive Substances; D014867:Water; D000641:Ammonia; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione