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@article{1411875, author = {Kučera, Jan and Netušilová, Julie and Sladeček, Stanislava and Kohutková Lánová, Martina and Vašíček, Ondřej and Štefková, Kateřina and Navrátilová, J. and Kubala, Lukáš and Pacherník, Jiří}, article_location = {London}, article_number = {July}, doi = {http://dx.doi.org/10.1155/2017/4386947}, keywords = {PROTEIN PHOSPHATASE 2A; CHLORIDE-INDUCED APOPTOSIS; INDUCIBLE FACTOR 1-ALPHA; MAP KINASE; SELF-RENEWAL; HIF-1-ALPHA ACCUMULATION; UNDIFFERENTIATED STATE; TYROSINE-PHOSPHATASE; REDOX-REGULATION; IRON CHELATOR}, language = {eng}, issn = {1942-0900}, journal = {Oxidative Medicine and Cellular Longevity}, title = {Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells}, volume = {2017}, year = {2017} }
TY - JOUR ID - 1411875 AU - Kučera, Jan - Netušilová, Julie - Sladeček, Stanislava - Kohutková Lánová, Martina - Vašíček, Ondřej - Štefková, Kateřina - Navrátilová, J. - Kubala, Lukáš - Pacherník, Jiří PY - 2017 TI - Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells JF - Oxidative Medicine and Cellular Longevity VL - 2017 IS - July SP - 1-16 EP - 1-16 PB - HINDAWI LTD SN - 19420900 KW - PROTEIN PHOSPHATASE 2A KW - CHLORIDE-INDUCED APOPTOSIS KW - INDUCIBLE FACTOR 1-ALPHA KW - MAP KINASE KW - SELF-RENEWAL KW - HIF-1-ALPHA ACCUMULATION KW - UNDIFFERENTIATED STATE KW - TYROSINE-PHOSPHATASE KW - REDOX-REGULATION KW - IRON CHELATOR N2 - Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1) is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES) cell maintenance. We employed wild-type and HIF-1 alpha-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O-2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected. Downregulation of ERK could not be mimicked either by pharmacologically induced hypoxia or by the overexpression. Dual-specificity phosphatases (DUSP) 1, 5, and 6 are hypoxia-sensitive MAPK-specific phosphatases involved in ERK downregulation, and protein phosphatase 2A (PP2A) regulates both ERK and Akt. However, combining multiple approaches, we revealed the limited significance of DUSPs and PP2A in the hypoxia-mediated attenuation of ERK signaling. Interestingly, we observed a decreased reactive oxygen species (ROS) level in hypoxia and a similar phosphorylation pattern for ERK when the cells were supplemented with glutathione. Therefore, we suggest a potential role for the ROS-dependent attenuation of ERK signaling in hypoxia, without the involvement of HIF-1. ER -
KUČERA, Jan, Julie NETUŠILOVÁ, Stanislava SLADEČEK, Martina KOHUTKOVÁ LÁNOVÁ, Ondřej VAŠÍČEK, Kateřina ŠTEFKOVÁ, J. NAVRÁTILOVÁ, Lukáš KUBALA and Jiří PACHERNÍK. Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells. \textit{Oxidative Medicine and Cellular Longevity}. London: HINDAWI LTD, 2017, vol.~2017, July, p.~1-16. ISSN~1942-0900. Available from: https://dx.doi.org/10.1155/2017/4386947.
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