Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) generated from inducible NO synthase (iNOS) during hepatic injury has been reported to contribute to cytoprotection or cellular damage. Rebamipide, anti-gastric ulcer drug, has protective effects in a variety of tissue and organ injury. However, it remains unknown whether rebamipide is involved in the regulation of iNOS gene expression under pathological conditions. We examined whether rebamipide influences the induction of iNOS in hepatocytes exposed to pro-inflammatory cytokine. Primary cultured rat hepatocytes were treated with interleukin (IL)-1beta in the presence or absence of rebamipide. Pretreatment of cells with rebamipide resulted in up-regulation of iNOS induction by IL-1beta, followed by increased NO production. Rebamipide enhanced the degradation of IkappaBalpha and the activation of NF-kappaB. Further, rebamipide super-induced the up-regulation of type I IL-1 receptor (IL-1RI), which is essential for iNOS induction in addition to the IkappaB/NF-kappaB pathway. Transfection experiments revealed that rebamipide increased the transactivation of iNOS promoter and the stability of iNOS mRNA. In the latter, rebamipide increased the antisense-transcript corresponding to the 3'-UTR of iNOS mRNA, which stabilizes iNOS mRNA by interacting with the 3'-UTR and RNA-binding proteins. These findings demonstrate that rebamipide up-regulates iNOS by iNOS promoter activation through NF-kappaB, and by its mRNA stabilization presumably through the super-induction of IL-1RI and antisense-transcript. Rebamipide may contribute to a novel potentiated treatment in liver injuries.
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PMID:Rebamipide, anti-gastric ulcer drug, up-regulates the induction of iNOS in proinflammatory cytokine-stimulated hepatocytes. 1793 43

A complex interaction of host genetic and environmental factors may be relevant in the development of Helicocobacter pylori-related gastric carcinogenesis. We investigated the effect of vascular endothelial growth factor (VEGF) gene polymorphisms on the risk of gastric cancer (GC) and peptic ulcer diseases in a Japanese population. The G1612A(rs10434) and C936T(rs3025039) polymorphisms in the 3' untranslated region (3'-UTR) of VEGF gene were genotyped in a total of 844 subjects including 385 GC, 143 ulcer including 98 gastric ulcer (GU), 45 duodenal ulcer (DU), and 316 nonulcer subjects. The 1612A carrier held a significantly higher risk of GC when compared to both noncancer and nonulcer (overall noncancer vs. GC; OR = 1.61, 95% CI = 1.17-2.21, P = 0.0038, nonulcer vs. GC; OR = 1.54, 95% CI = 1.07-2.22, P = 0.0197). The 1612A carrier was more closely associated with an increased risk of noncardiac cancer (OR = 1.64, 95% CI = 0.17-2.21, P = 0.0038), lower third cancer (OR = 1.97, 95% CI = 1.30-3.00, P = 0.002), and Lauren's diffuse-type cancer (OR = 1.75, 95% CI = 1.24-2.46, P = 0.001), while the same genotype was not associated with the progression of GC. The C936T genotype was not associated with a risk of GC and its progression. Both the G1612A and C936T genotypes were not associated with the risk of peptic ulcer diseases. Our data suggest that the G1612A, but not C936T polymorphisms in the 3'-UTR of VEGF gene is associated with the susceptibility to GC in the Japanese population.
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PMID:Effect of polymorphisms in the 3' untranslated region (3'-UTR) of vascular endothelial growth factor gene on gastric cancer and peptic ulcer diseases in Japan. 1949 79