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. 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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Basic information
Original name Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells
Authors KUČERA, Jan (203 Czech Republic, belonging to the institution), Julie NETUŠILOVÁ (203 Czech Republic, belonging to the institution), Stanislava SLADEČEK (688 Serbia, belonging to the institution), Martina KOHUTKOVÁ LÁNOVÁ (203 Czech Republic, belonging to the institution), Ondřej VAŠÍČEK (203 Czech Republic), Kateřina ŠTEFKOVÁ (203 Czech Republic, belonging to the institution), J. NAVRÁTILOVÁ (203 Czech Republic), Lukáš KUBALA (203 Czech Republic) and Jiří PACHERNÍK (203 Czech Republic, guarantor, belonging to the institution).
Edition Oxidative Medicine and Cellular Longevity, London, HINDAWI LTD, 2017, 1942-0900.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10601 Cell biology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 4.936
RIV identification code RIV/00216224:14310/17:00100432
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1155/2017/4386947
UT WoS 000406334700001
Keywords in English 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
Tags NZ, rivok
Tags International impact, Reviewed
Changed by Changed by: Ing. Nicole Zrilić, učo 240776. Changed: 5/4/2018 09:52.
Abstract
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.
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