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Hypoxia Downregulates MAPKERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells
Joint Authors
Kučera, Jan
Netušilová, Julie
Sladeček, Stanislava
Lánová, Martina
Vašíček, Ondřej
Štefková, Kateřina
Navrátilová, Jarmila
Pacherník, J.
Kubala, Lukas
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-07-27
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
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-1α-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways.
Cultivation in 1% O2 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.
American Psychological Association (APA)
Kučera, Jan& Netušilová, Julie& Sladeček, Stanislava& Lánová, Martina& Vašíček, Ondřej& Štefková, Kateřina…[et al.]. 2017. Hypoxia Downregulates MAPKERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1194708
Modern Language Association (MLA)
Kučera, Jan…[et al.]. Hypoxia Downregulates MAPKERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-16.
https://search.emarefa.net/detail/BIM-1194708
American Medical Association (AMA)
Kučera, Jan& Netušilová, Julie& Sladeček, Stanislava& Lánová, Martina& Vašíček, Ondřej& Štefková, Kateřina…[et al.]. Hypoxia Downregulates MAPKERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1194708
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1194708