Počet záznamů: 1  

Background Levels of Neomorphic 2-hydroxyglutarate Facilitate Proliferation of Primary Fibroblasts

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    0482863 - FGÚ 2018 RIV CZ eng J - Článek v odborném periodiku
    Dvořák, Aleš - Zelenka, Jaroslav - Smolková, Katarína - Vítek, L. - Ježek, Petr
    Background Levels of Neomorphic 2-hydroxyglutarate Facilitate Proliferation of Primary Fibroblasts.
    Physiological Research. Roč. 66, č. 2 (2017), s. 293-304. ISSN 0862-8408. E-ISSN 1802-9973
    Grant CEP: GA ČR(CZ) GPP301/12/P381; GA ČR(CZ) GA16-04788S
    Institucionální podpora: RVO:67985823
    Klíčová slova: 2-hydroxyglutarate * fibroblast proliferation * SH-SY5Y neuroblastoma cells
    Obor OECD: Oncology
    Impakt faktor: 1.324, rok: 2017

    Each cell types or tissues contain certain “physiological” levels of R-2-hydroxyglutarate (2HG), as well as enzymes for its synthesis and degradation. 2HG accumulates in certain tumors, possessing heterozygous point mutations of isocitrate dehydrogenases IDH1 (cytosolic) or IDH2 (mitochondrial) and contributes to strengthening their malignancy by inhibiting 2-oxoglutaratedependent dioxygenases. By blocking histone de-methylation and 5-methyl-cytosine hydroxylation, 2HG maintains cancer cells de-differentiated and promotes their proliferation. However, physiological 2HG formation and formation by non-mutant IDH1/2 in cancer cells were neglected. Consequently, low levels of 2HG might play certain physiological roles. We aimed to elucidate this issue and found that compared to highest 2HG levels in hepatocellular carcinoma HepG2 cells and moderate levels in neuroblastoma SH-SY5Y cells, rat primary fibroblast contained low basal 2HG levels at early passages. These levels increased at late passage and likewise 2HG/2OG ratios dropped without growth factors and enormously increased at hypoxia, reaching levels compared to cancer HepG2 cells. Responses in SH-SY5Y cells were opposite. Moreover, external 2HG supplementation enhanced fibroblast growth. Hence, we conclude that low 2HG levels facilitate cell proliferation in primary fibroblasts, acting via hypoxia-induced factor regulations and epigenetic changes.
    Trvalý link: http://hdl.handle.net/11104/0278254

     
     
Počet záznamů: 1  

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