Mucosal acidification increases hydrogen sulfide release through up-regulating gene and protein expressions of cystathionine gamma-lyase in the rat gastric mucosa

Abstract

<strong><em>Objective(s):</em></strong> This study was performed to investigate the effects of mucosal acidification on mRNA expression and protein synthesis of cystathionine gamma lyase (CSE), cystathionine beta synthase (CBS), and mucosal release of H₂S in gastric mucosa in rats. <strong><em>Materials and Methods:</em></strong>Thirty-two rats were randomly assigned into 4 groups (8 in each), including: the control group, HCl (10 mM) treated group, HCl (100 mM) treated group, and one group to study the effect of Nω-Nitro-L-arginine methyl ester hydrochloride<strong> </strong>(L-NAME). Anesthetized rats underwent tracheostomy and midline laparotomy. Ninety min after the instillation of neutral or acidic solutions, animals were sacrificed and the gastric mucosa was collected to measure the H₂S concentration by ELISA method and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR (qRT-PCR). Protein synthesis was also detected by Western blot method. <strong><em>Results:</em></strong>Mucosal acidification with 10 and 100 HCl, significantly increased mucosal levels of H₂S (<em>P</em><0.01 and <em>P</em><0.001) and mRNA (<em>P</em><0.01 and <em>P</em><0.001) and protein expressions of CSE (<em>P</em><0.01 and <em>P</em><0.001). L-NAME treatment reversed H₂S release to control level. <strong><em>Conclusion:</em></strong>Our findings indicated that mucosal acidification with HCl increased mucosal release of H₂S through upregulation of CSE gene and its protein expression. This effect is mainly mediated through the involvement of nitric oxide.