title: Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.
abstract: Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.
authors.affiliation: Department of Pediatrics, Medical College of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Pediatrics, Medical College of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Renmin
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Medical College of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Guorui
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, Medical College of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Digestive Disease, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Digestive Disease, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Digestive Disease, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Digestive Disease, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005750:Gastric Juice / Q000737:chemistry / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006657:Histones / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D013276:Stomach Ulcer / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D013312:Stress, Physiological; D013315:Stress, Psychological
chemical_list: D000893:Anti-Inflammatory Agents; D006657:Histones; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase; D003474:Curcumin