Dysregulation of gastric H,K-ATPase by cigarette smoke extract.
OBJECTIVE
To test whether the expression and activity of H,K-ATPase in parietal cells would be affected by cigarette smoke extract.


METHODS
Extracts of cigarette smoke were administered into mice by gastric gavage (5 mg/kg body weight/day) for 3 d or in drinking water for 7 or 14 d. For the latter, each day a mouse consumed 5 mL water containing extracts of two cigarettes, on average. Control littermate mice received only vehicle. To compare the amount of H,K-ATPase in control and smoke-treated mice, the stomach was processed for Western blotting and immunohistochemical analysis using monoclonal antibodies specific for alpha- or beta-subunits of H,K-ATPase. The p-nitrophenylphosphatase activity assay was used as a measurement for K-dependent H,K-ATPase activity.


RESULTS
Probed transblots showed an increase in the amount of H,K-ATPase in smoke-treated mice which was confirmed by immunohistochemistry and was found to be due to increased amounts of protein per parietal cell rather than an increased parietal cell number. The increase in the amount of H,K-ATPase was associated with an enhancement of its enzymatic activity. K-dependent activity in control and smoke-treated mice was significantly different (respectively, 0.12 micromol/mg vs 0.27 micromol/mg per minute, P < 0.05).


CONCLUSIONS
Administration of cigarette smoke extract is associated with an increase in the amount and activity of H,K-ATPase and hence, smokers are susceptible to development of peptic ulcer.
Hammadi
Muna
M
Department of Anatomy, Faculty of Medicine & Health Sciences, UAE University, Al-Ain, PO Box 17666, United Arab Emirates.
Adi
Mohamed
M
John
Rony
R
Khoder
Ghalia A K
GA
Karam
Sherif M
SM
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D010437:Peptic Ulcer / Q000209:etiology; D012907:Smoking / Q000009:adverse effects*; D013270:Stomach / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D014026:Nicotiana / Q000009:adverse effects
D017506:H(+)-K(+)-Exchanging ATPase
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