Effect Of Curcumin Inhibits Histone Acetylation On The H+,K+-ATPase Gene Transcriptional Expression

Background and object:With the popularity of endoscopic techniques and applications in the field of paediatrics, peptic ulcer in children incidence has an increasing trend in recent years. Most studies suggest that stress gastric ulcer is related to gastric mucosal barrier damage and gastric acid, especially abnormal secretion of gastric acid, plays an important role in the development of stress gastric ulcer. And the gastric acid secretion is closely related with H+,K+-ATPase activity in gastric parietal cells. The use of acid-suppressing drugs is the key to treatment in children’s peptic ulcer, but excessive use of acid-suppressing drugs can cause damage to the environment of gastric acid, which increases the risk of infection probability. Curcumin is a novel anti-ulcer drugs, with economy, security, the advantages of no significant adverse reactions and rich resources, therefore it has a good prospect for clinical application. And the studies found that curcumin had a strong inhibitory activity on H+,K+-ATPase, and the gene transcription and expression on H+,K+-ATPase in gastric parietal cell is related to histone acetylation, meanwhile some studies also found curcumin had a strong role on histone modifications. Therefore to investigate the effect of curcumin inhibits the H+,K+-ATPase gene transcription and expression at histone acetylation levels in vivo.Methods:Forty male SD rats were divided into 4 groups, control group, ulcer model group, curcumin group and ursodesoxycholic acid (UDAC) group, randomly. The gastric mucosa ulcer index (UI) and gastric juice pH and histopathological changes in gastric mucosa were measured. The gene transcription and expression levels H+,K+-ATPase alpha(a)subunit were detected by RT-PCR and Western Blot. Meanwhile, the level of acetylated histone H3 at the site of H+,K+-ATPase promoter gene was examined by chromatin immunoprecipitation assay. The results were analyzed with the Software of SPSS 16.0.Results:Compared with control group, the UI and H+,K+-ATPase a subunit mRNA gene expression increased significantly(P<0.01), and pH value decreased significantly (P<0.01) in ulcer model group. Gastric mucosal hemorrhage and ulcer were observed under light microscope in ulcer model group. Gastric H+,K+-ATPase a subunit protein and total acetylated histone H3 upregulated significantly and histone H3 at the site of H+,K+-ATPase promoter acetylation levels were significantly increased in ulcer model group. Compared with ulcer model group, the UI and H+,K+-ATPase a subunit mRNA gene expression decreased significantly (P<0.01), and pH value increased significantly(P<0.01) in curcumin group. Gastric H+,K+-ATPase a subunit protein and total acetylated histone H3 downregulated significantly and histone H3 at the site of H+,K+-ATPase promoter acetylation levels were significantly decreased in curcumin group. There were no significant difference of UI, pH value, gastric H+,K+-ATPase a subunit protein and total acetylated histone H3, H+,K+-ATPase mRNA and histone H3 at the site of H+,K+-ATPase promoter acetylation levels between curcumin group and ursodeoxycholic acid group.Conclusions:Curcumin can reduce gastric acid secretion effectively in rats, it has a good protective effect on gastric mucosa. Further studies showed that curcumin could weaken the acetylation of histone H3 at the site of H+,K+-ATPase promoter gene, inhibit transcription and expression of H+,K+-ATPase gene, which suggested it was possible relevant about curcumin inhibited parietal cells H+,K+-ATPase mRNA transcription and expressions and its inhibition of histone acetylation. Therefore one of the mechanisms on the antiulcer of curcumin was related to its effect of epigenetic modificative.