The stabilization of hypoxia inducible factor modulates differentiation status and inhibits the proliferation of mouse embryonic stem cells

0457707 - BFÚ 2016 RIV IE eng J - Journal Article
Binó, Lucia - Kučera, J. - Štefková, K. - Šindlerová, Lenka - Lanová, M. - Kudová, J. - Kubala, Lukáš - Pachernik, J.
The stabilization of hypoxia inducible factor modulates differentiation status and inhibits the proliferation of mouse embryonic stem cells.
Chemico-Biological Interactions. Roč. 244, JAN2016 (2016), s. 204-214. ISSN 0009-2797. E-ISSN 1872-7786
R&D Projects: GA MŠMT(CZ) EE2.3.30.0030
Institutional support: RVO:68081707
Keywords : Hypoxia * HIF-1 * Prolyl hydroxylase
Subject RIV: BO - Biophysics
Impact factor: 3.143, year: 2016

ypoxic conditions are suggested to affect the differentiation status of stem cells (SC), including embryonic stem cells (ESC). Hypoxia inducible factor (HIF) is one of the main intracellular molecules responsible for the cellular response to hypoxia. Hypoxia stabilizes HIF by inhibiting the activity of HIF prolyl-hydroxylases (PHD), which are responsible for targeting HIF-alpha subunits for proteosomal degradation. To address the impact of HIF stabilization on the maintenance of the stemness signature of mouse ESC (mESC), we tested the influence of the inhibition of PHDs and hypoxia (1% O-2 and 5% O-2) on spontaneous ESC differentiation triggered by leukemia inhibitory factor withdrawal for 24 and 48 h. The widely used panhydroxylase inhibitor dimethyloxaloylglycine (DMOG) and PHD inhibitor JNJ-42041935 (JNJ) with suggested higher specificity towards PHDs were employed. Both inhibitors and both levels of hypoxia significantly increased HIF-1alpha and HIF-2alpha protein levels and HIF transcriptional activity in spontaneously differentiating mESC.
Permanent Link: http://hdl.handle.net/11104/0258109