Background levels of neomorphic 2-hydroxyglutarate facilitate proliferation of primary fibroblasts

Title:

Background levels of neomorphic 2-hydroxyglutarate facilitate proliferation of primary fibroblasts

Creator:

Dvořák, A., Jaroslav Zelenka, Katarína Smolková, Libor Vítek, and Petr Ježek

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:312676ff-61bc-46fd-9a22-43fc52fd542c
uuid:312676ff-61bc-46fd-9a22-43fc52fd542c
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, 2-hydroxyglutarate, fibroblast proliferation, SH-SY5Y neuroblastoma cells, 14, and 612

Type:

article, články, journal articles, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

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., A. Dvořák, J. Zelenka, K. Smolková, L. Vítek, P. Ježek., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2017 Volume:66 | Number:2

Harvested from:

CDK

Metadata only:

false