Other formats:
BibTeX
LaTeX
RIS
@proceedings{1138591,
author = {Musilová, Julie and Kučera, Jan and Lánová, Martina and Štefková, Kateřina and Kubala, Lukáš and Pacherník, Jiří},
booktitle = {Stem Cells and Cell therapy: From research to modern clinical application},
keywords = {hypoxia stem cells HIF},
language = {eng},
title = {The mechanisms of response to hypoxia in embryonic stem cells},
url = {http://www.symma.cz/baria/down/abstrakta_2013.pdf},
year = {2013}
}
TY - CONF
ID - 1138591
AU - Musilová, Julie - Kučera, Jan - Lánová, Martina - Štefková, Kateřina - Kubala, Lukáš - Pacherník, Jiří
PY - 2013
TI - The mechanisms of response to hypoxia in embryonic stem cells
KW - hypoxia stem cells HIF
UR - http://www.symma.cz/baria/down/abstrakta_2013.pdf
N2 - Oxygen is a crucial element for life of most organisms. Key regulator of oxygen sensing and responding intracellular machinery is heterodimeric transcription factor HIF1 (hypoxia inducible factor 1). Presence of oxygen leads to rapid ubiquitination and proteozomal degradation of cytoplasmic subunit HIF1alpha. This process is abolished in hypoxia, leading to accumulation of alpha subunit and dimerization with HIF1beta (also called ARNT). Upon binding of HIF1 heterodimer to hypoxia responsive elements, transcription of many specific genes involved in oxygen homeostasis is induced (Wang et al., 1995). Moreover hypoxia increases a production of intracellular reactive oxygen species (ROS) (Chandel et al., 2002). ROS can modulate cell signaling through transcription and also through posttranslational modifications of intracellular signaling pathways (Finkel, 2011). Additionally, further mechanisms of low oxygen sensing excluding the involvement of HIF and ROS were reported (Wouters and Koritzinsky, 2008). Thus, so called hypoxia signaling could be promoted via different HIF and ROS dependent and independent manners. Since hypoxia is known to regulate stem cell fate both in vivo and in vitro, the main aim of our study is to clarify the role of HIF and ROS in hypoxic response of embryonic stem cell. We used wild-type and HIF1alpha deficient (-/-) mouse embryonic stem cell (mES) to analyze signaling pathways responsible for stemness maintenance. We compared effects of hypoxia (1% O2) and pharmacologically induced stabilization of HIF in normoxic conditions on mES signaling. To clarify effects of ROS, various redox modulators were involved in our study. Posttranslational modifications of JAK/STAT3, MEK/ERK, PI3K/Akt, p38 and Notch signaling cascades were analyzed, as well as effects on proliferation, differentiation and apoptosis these mES cells. Our data show HIF1alpha and ROS-dependent down regulation of MEK/ERK signaling under hypoxic conditions. On the other hand, either hypoxia or ROS scavengers do not affect activation of JAK/STAT3 signaling. Activities of PI3K/Akt and p38 signaling pathways were downregulated independently on HIF1alpha or ROS. Interestingly, the pharmacological inhibition of prolylhydroxylases, which leads to increase of HIF1 stability in normoxia, does not affect any analyzed signaling pathways. In conclusion, our results clearly document the complexity of cellular responses to hypoxic conditions, where the important part of such responses is HIF1alpha independent.
ER -
MUSILOVÁ, Julie, Jan KUČERA, Martina LÁNOVÁ, Kateřina ŠTEFKOVÁ, Lukáš KUBALA and Jiří PACHERNÍK. The mechanisms of response to hypoxia in embryonic stem cells (The mechanism of response to hypoxia in embryonic stem cells). In \textit{Stem Cells and Cell therapy: From research to modern clinical application}. 2013.
|
