TXNIP regulates AKT-mediated cellular senescence by direct interaction under glucose-mediated metabolic stress

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dc.contributor.authorHangsak Huy-
dc.contributor.authorHae-Young Song-
dc.contributor.authorMi Jeong Kim-
dc.contributor.authorWon Sam Kim-
dc.contributor.authorDong Oh Kim-
dc.contributor.authorJae-Eun Byun-
dc.contributor.authorJungwoon Lee-
dc.contributor.authorYoung-Jun Park-
dc.contributor.authorTae-Don Kim-
dc.contributor.authorSuk Ran Yoon-
dc.contributor.authorE J Choi-
dc.contributor.authorChul-Ho Lee-
dc.contributor.authorJi-Yoon Noh-
dc.contributor.authorHaiyoung Jung-
dc.contributor.authorIn Pyo Choi-
dc.date.accessioned2019-01-23T16:30:53Z-
dc.date.available2019-01-23T16:30:53Z-
dc.date.issued2018-
dc.identifier.issn14749718-
dc.identifier.uri10.1111/acel.12836ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/18233-
dc.description.abstractAging is associated with an inevitable and universal loss of cell homeostasis and restricts an organism's lifespan by an increased susceptibility to diseases and tissue degeneration. The glucose uptake associated with producing energy for cell survival is one of the major causes of ROS production under physiological conditions. However, the overall mechanisms by which glucose uptake results in cellular senescence remain mysterious. In this study, we found that TXNIP deficiency accelerated the senescent phenotypes of MEF cells under high glucose condition. TXNIP-/- MEF cells showed greater induced glucose uptake and ROS levels than wild-type cells, and N-acetylcysteine (NAC) treatment rescued the cellular senescence of TXNIP-/- MEF cells. Interestingly, TXNIP-/- MEF cells showed continuous activation of AKT during long-term subculture, and AKT signaling inhibition completely blocked the cellular senescence of TXNIP-/- MEF cells. In addition, we found that TXNIP interacted with AKT via the PH domain of AKT, and their interaction was increased by high glucose or H2 O2 treatment. The inhibition of AKT activity by TXNIP was confirmed using western blotting and an in vitro kinase assay. TXNIP deficiency in type 1 diabetes mice (Akita) efficiently decreased the blood glucose levels and finally increased mouse survival. However, in normal mice, TXNIP deficiency induced metabolic aging of mice and cellular senescence of kidney cells by inducing AKT activity and aging-associated gene expression. Altogether, these results suggest that TXNIP regulates cellular senescence by inhibiting AKT pathways via a direct interaction under conditions of glucose-derived metabolic stress.-
dc.publisherWiley-
dc.titleTXNIP regulates AKT-mediated cellular senescence by direct interaction under glucose-mediated metabolic stress-
dc.title.alternativeTXNIP regulates AKT­mediated cellular senescence by direct interaction under glucose­mediated metabolic stress-
dc.typeArticle-
dc.citation.titleAging Cell-
dc.citation.number6-
dc.citation.endPagee12836-
dc.citation.startPagee12836-
dc.citation.volume17-
dc.contributor.affiliatedAuthorHangsak Huy-
dc.contributor.affiliatedAuthorHae-Young Song-
dc.contributor.affiliatedAuthorMi Jeong Kim-
dc.contributor.affiliatedAuthorWon Sam Kim-
dc.contributor.affiliatedAuthorDong Oh Kim-
dc.contributor.affiliatedAuthorJae-Eun Byun-
dc.contributor.affiliatedAuthorJungwoon Lee-
dc.contributor.affiliatedAuthorYoung-Jun Park-
dc.contributor.affiliatedAuthorTae-Don Kim-
dc.contributor.affiliatedAuthorSuk Ran Yoon-
dc.contributor.affiliatedAuthorChul-Ho Lee-
dc.contributor.affiliatedAuthorJi-Yoon Noh-
dc.contributor.affiliatedAuthorHaiyoung Jung-
dc.contributor.affiliatedAuthorIn Pyo Choi-
dc.contributor.alternativeName허이항삭-
dc.contributor.alternativeName송해영-
dc.contributor.alternativeName김미정-
dc.contributor.alternativeName김원삼-
dc.contributor.alternativeName김동오-
dc.contributor.alternativeName변재은-
dc.contributor.alternativeName이정운-
dc.contributor.alternativeName박영준-
dc.contributor.alternativeName김태돈-
dc.contributor.alternativeName윤석란-
dc.contributor.alternativeName최은지-
dc.contributor.alternativeName이철호-
dc.contributor.alternativeName노지윤-
dc.contributor.alternativeName정해용-
dc.contributor.alternativeName최인표-
dc.identifier.bibliographicCitationAging Cell, vol. 17, no. 6, pp. e12836-e12836-
dc.identifier.doi10.1111/acel.12836-
dc.subject.keywordAKT-
dc.subject.keywordTXNIP-
dc.subject.keywordaging-
dc.subject.keywordglucose-
dc.subject.keywordreactive oxygen species-
dc.subject.localAKT-
dc.subject.localAkt-
dc.subject.localTXNIP-
dc.subject.localaging-
dc.subject.localAging-
dc.subject.localglucose-
dc.subject.localGlucose-
dc.subject.localreactive oxygen species-
dc.subject.localReactive oxygen species (ROS)-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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