Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in
ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic
Stem Cells

J 2017

Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells

KUČERA, Jan, Julie NETUŠILOVÁ, Stanislava SLADEČEK, Martina KOHUTKOVÁ LÁNOVÁ, Ondřej VAŠÍČEK et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Abstract

V originále

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.

Citovat

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.

@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.

Detailed Information on Publication Record