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dc.creatorEleftheriadis, T.en
dc.creatorPissas, G.en
dc.creatorAntoniadi, G.en
dc.creatorLiakopoulos, V.en
dc.creatorStefanidis, I.en
dc.date.accessioned2015-11-23T10:26:12Z
dc.date.available2015-11-23T10:26:12Z
dc.date.issued2015
dc.identifier10.3892/etm.2015.2763
dc.identifier.issn17920981
dc.identifier.urihttp://hdl.handle.net/11615/27332
dc.description.abstractActivated T cells rely on aerobic glycolysis and glutaminolysis in order to proliferate and differentiate into effector cells. Therefore, intervention in these metabolic pathways inhibits proliferation. The aim of the present study was to evaluate the effects of Krebs' cycle inhibition at the level of malate dehydrogenase‑2 (MDH2) in human activated T cells using the MDH2 inhibitor LW6. Activated T cells from healthy volunteers were cultured in the presence or absence of LW6 and cytotoxicity, cell proliferation and the expression levels of hypoxia‑inducible factor (HIF)‑1α, c‑Myc, p53, cleaved caspase‑3 and certain enzymes involved in glucose metabolism and glutaminolysis were evaluated. The results revealed that LW6 was not toxic and decreased apoptosis and the levels of the pro‑apoptotic tumor suppressor p53. In addition, LW6 inhibited T‑cell proliferation and decreased the levels of c‑Myc, HIF‑1α, glucose transporter‑1, hexokinase‑II, lactate dehydrogenase‑A and phosphorylated pyruvate dehydrogenase. By contrast, LW6 increased the levels of pyruvate dehydrogenase. These alterations may lead to decreased production of pyruvate, which preferentially enters into the Krebs' cycle. Furthermore, LW6 decreased the levels of glutaminase‑2, while increasing those of glutaminase‑1, which may preserve glutaminolysis, and possibly pyruvate‑malate cycling, potentially protecting the cells from energy collapse. In summary, the inhibition of MDH2 in activated T cells abrogates proliferation without adversely affecting cell survival. Adaptations of cellular glucose and glutamine metabolism may prevent energy collapse. © 2015, Spandidos Publications. All rights reserved.en
dc.source.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-84942253389&partnerID=40&md5=ff10a54ed8707b7000ad99833e113c0d
dc.subjectApoptosisen
dc.subjectGlucose metabolismen
dc.subjectGlutaminolysisen
dc.subjectMalate dehydrogenaseen
dc.subjectProliferationen
dc.subjectT cellen
dc.subjectcaspase 3en
dc.subjectenzyme inhibitoren
dc.subjectglucose transporter 1en
dc.subjecthexokinaseen
dc.subjecthypoxia inducible factor 1alphaen
dc.subjectlactate dehydrogenaseen
dc.subjectmalate dehydrogenase 2 inhibitoren
dc.subjectMyc proteinen
dc.subjectpolyvinylidene fluorideen
dc.subjectprotein p53en
dc.subjectpyruvate dehydrogenaseen
dc.subjectunclassified drugen
dc.subjectadulten
dc.subjectantiproliferative activityen
dc.subjectArticleen
dc.subjectcell survivalen
dc.subjectcitric acid cycleen
dc.subjectclinical articleen
dc.subjectcontrolled studyen
dc.subjectcytotoxicityen
dc.subjectenzyme linked immunosorbent assayen
dc.subjectfemaleen
dc.subjectglycolysisen
dc.subjecthumanen
dc.subjecthuman cellen
dc.subjectimmunostimulationen
dc.subjectlymphocyte proliferationen
dc.subjectmaleen
dc.subjectprotein expressionen
dc.subjectprotein phosphorylationen
dc.subjectT lymphocyteen
dc.subjectWestern blottingen
dc.subjectXTT assayen
dc.titleMalate dehydrogenase-2 inhibitor LW6 promotes metabolic adaptations and reduces proliferation and apoptosis in activated human T-cellsen
dc.typejournalArticleen


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