Expression and activities of three inducible enzymes in the healing of gastric ulcers in rats.
OBJECTIVE
To explore the roles of nitric oxide synthase (NOS), heme oxygenase (HO) and cyclooxygenase (COX) in gastric ulceration and to investigate the relationships of the expression and activities of these enzymes at different stages of gastric ulceration.


METHODS
Gastric ulcers (kissing ulcers) were induced by luminal application of acetic acid. Gastric tissue samples were obtained from the ulcer base, ulcer margin, and non-ulcerated area around the ulcer margin at different time intervals after ulcer induction. The mRNA expression and protein levels of inducible and constitutive isoforms of NOS, HO and COX were analyzed with RT-PCR and Western blotting methods. The activities of the total NOS, inducible NOS (iNOS), HO, and COX were also determined.


RESULTS
Differential expression of inducible iNOS, HO-1 and COX-2 and enzyme activities of NOS, HO and COX were found in the gastric ulcer base. High iNOS expression and activity were observed on day 1 to day 3 in severely inflamed ulcer tissues. Maximum expressions of HO-1 and COX-2 and enzyme activities of HO and COX lagged behind that of iNOS, and remained at high levels during the healing phase.


CONCLUSIONS
The expression and activities of inducible NOS, HO-1 and COX-2 are found to be correlated to different stages of gastric ulceration. Inducible NOS may contribute to ulcer formation while HO-1 and COX-2 may promote ulcer healing.
Guo
Jin-Sheng
JS
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
Cho
Chi-Hin
CH
Wang
Wei-Ping
WP
Shen
Xi-Zhong
XZ
Cheng
Chuen-Lung
CL
Koo
Marcel Wing Leung
MW
D000818:Animals; D051546:Cyclooxygenase 2; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000201:enzymology / Q000503:physiopathology*; D014945:Wound Healing
D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases