A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in protective effect of the proton pump inhibitor pantoprazole against indomethacin-induced gastric damage in rats
DC Field | Value | Language |
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dc.contributor.author | Lee, Ho-Jae | - |
dc.contributor.author | Han, Young-Min | - |
dc.contributor.author | Kim, Eun-Hee | - |
dc.contributor.author | Kim, Yoon-Jae | - |
dc.contributor.author | Hahm, Ki-Baik | - |
dc.date.available | 2020-02-29T04:47:48Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2012-10-16 | - |
dc.identifier.issn | 1471-230X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16083 | - |
dc.description.abstract | Background: Proton pump is an integral membrane protein that is ubiquitous ATP binding cassette (ABC) involved in many transport processes in all living organisms, among which a specialized form of pump, so called p-type proton pump, exists in the parietal cells of stomach. Though proton pump inhibitors (PPIs) are frequently prescribed to prevent nonsteroidal anti-inflammatory drugs (NSAIDs)-induced gastric damage, the acid suppressive actions do not suffice to explain. Methods: In order to document the effects of pantoprazole, one of PPIs, on the NSAIDs-induced gastric damage, in vitro and in vivo studies were performed. Immunocytochemistry, Western blot analysis, electrophoretic mobility shift assay and RT-PCR were conducted to evaluate the induction of heme oxygenase-1 (HO-1) through Nrf2 activation in normal gastric mucosal RGM-1 cells or in vivo stomach tissues from rats treated with indomethacin and/or pantoprazole. Results: Pantoprazole activated Nrf2 through inactivation of Keap1, after which the expression of HO-1 was significantly increased in a dose-dependent manner in RGM-1 cells. Increased ARE-DNA binding activity was observed maximally at 1 h with 300 mu M of pantoprazole. The expression of HO-1 induced by pantoprazole was significantly associated with the increased in vitro tube formation (P < 0.05) and angiogenic factors including VEGF, bFGF, and HIF-1 alpha. Indomethacin markedly increased the expressions of TNF-alpha, IL-1 beta, IL-8, NOX-1, ICAM-1 and VCAM, whereas pantoprazole significantly decreased the expressions of indomethacin-induced these inflammatory mediators in accord with pantoprazole-induced HO-1 (P < 0.05) as documented with HO-1 inhibitor. In vivo model of indomethacin-induced gastric damage could validate in vitro-drawn results that pantoprazole remarkably protected against indomethacin-induced gastric damage, in which zinc protoporphyrin (5 mg/kg, ip) significantly abolished the protective efficacy of pantoprazole. Conclusion: These results demonstrate that Nrf2-mediated HO-1 induction of PPIs afforded a significant protective effect against NSAIDs-induced gastric damage beyond acid suppressive actions. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.relation.isPartOf | BMC GASTROENTEROLOGY | - |
dc.subject | NONSTEROIDAL ANTIINFLAMMATORY DRUGS | - |
dc.subject | COST-EFFECTIVENESS | - |
dc.subject | KAPPA-B | - |
dc.subject | LANSOPRAZOLE | - |
dc.subject | PREVENTION | - |
dc.subject | MECHANISMS | - |
dc.subject | STRATEGIES | - |
dc.subject | INJURY | - |
dc.subject | ACTIVATION | - |
dc.subject | REDUCTION | - |
dc.title | A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in protective effect of the proton pump inhibitor pantoprazole against indomethacin-induced gastric damage in rats | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000314352900001 | - |
dc.identifier.doi | 10.1186/1471-230X-12-143 | - |
dc.identifier.bibliographicCitation | BMC GASTROENTEROLOGY, v.12 | - |
dc.identifier.scopusid | 2-s2.0-84867421023 | - |
dc.citation.title | BMC GASTROENTEROLOGY | - |
dc.citation.volume | 12 | - |
dc.contributor.affiliatedAuthor | Lee, Ho-Jae | - |
dc.contributor.affiliatedAuthor | Kim, Yoon-Jae | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Heme oxygenase-1 | - |
dc.subject.keywordAuthor | Proton pump inhibitor | - |
dc.subject.keywordAuthor | NSAIDs-induced gastropathy | - |
dc.subject.keywordAuthor | Nrf2 | - |
dc.subject.keywordPlus | NONSTEROIDAL ANTIINFLAMMATORY DRUGS | - |
dc.subject.keywordPlus | COST-EFFECTIVENESS | - |
dc.subject.keywordPlus | KAPPA-B | - |
dc.subject.keywordPlus | LANSOPRAZOLE | - |
dc.subject.keywordPlus | PREVENTION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | STRATEGIES | - |
dc.subject.keywordPlus | INJURY | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | REDUCTION | - |
dc.relation.journalResearchArea | Gastroenterology & Hepatology | - |
dc.relation.journalWebOfScienceCategory | Gastroenterology & Hepatology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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