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Antioxidant modifications induced by the new metformin derivative HL156A regulate metabolic reprogramming in SAMP1/kl (-/-) mice

DC FieldValueLanguage
dc.contributor.author육종인-
dc.date.accessioned2019-02-14T01:52:31Z-
dc.date.available2019-02-14T01:52:31Z-
dc.date.issued2018-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/167267-
dc.description.abstractAging is characterized by a reduced ability to defend against stress, an inability to maintain homeostasis, and an increased risk of disease. In this study, a metabolomics approach was used to identify novel metabolic pathways that are perturbed in a mouse model of accelerated aging (SAMP1/kl-/-) and to gain new insights into the metabolic associations of the metformin derivative HL156A. Extensive inflammation and calcification were observed in the tissues of the SAMP1/kl-/- mice with premature aging. In mouse embryonic fibroblasts (MEFs) obtained from SAMP1/kl-/- mice, we observed that HL156A induced FOXO1 expression through inhibition of the IGF-1/AKT/mTOR signaling pathways. Treatment of HL156A decreased reactive oxygen species production and enhanced mitochondrial transmembrane potential in SAMP1/kl-/- MEFs. A metabolomic profile analysis showed that HL156A increased the GSH/GSSG ratio in the kidneys of SAMP1/kl-/- mice (8-12 weeks old). In addition, treating SAMP1/kl-/- mice with HL156A (30 mg/kg) for 4 weeks improved survival and decreased the significant elevation of oxidized GSH (GSSG) that was observed in SAMP1/kl-/- mice. In histological sections, HL156A administered SAMP1/kl-/- mice exhibited a decrease in excessive calcification. Based on these findings, we conclude that the new metformin derivative HL156A may inhibit oxidative damage by inducing glutathione metabolism and antioxidant pathways.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherImpact Journals-
dc.relation.isPartOfAging-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleAntioxidant modifications induced by the new metformin derivative HL156A regulate metabolic reprogramming in SAMP1/kl (-/-) mice-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Pathology (구강병리학교실)-
dc.contributor.googleauthorSoo-A Kim-
dc.contributor.googleauthorThuy Giang Lam-
dc.contributor.googleauthorJong-In Yook-
dc.contributor.googleauthorSang-Gun Ahn-
dc.identifier.doi10.18632/aging.101549-
dc.contributor.localIdA02536-
dc.relation.journalcodeJ03575-
dc.identifier.eissn1945-4589-
dc.identifier.pmid30222592-
dc.subject.keywordHL156A-
dc.subject.keywordSAMP1/ Klotho-
dc.subject.keywordaging-
dc.subject.keywordantioxidant-
dc.subject.keywordglutathione-
dc.subject.keywordmetabolic profiling-
dc.contributor.alternativeNameYook, Jong In-
dc.contributor.affiliatedAuthor육종인-
dc.citation.volume10-
dc.citation.number9-
dc.citation.startPage2338-
dc.citation.endPage2355-
dc.identifier.bibliographicCitationAging, Vol.10(9) : 2338-2355, 2018-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers

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