Arachidonic acid release by H2O2 mediated proliferation of mouse embryonic stem cells: Involvement of Ca2+/PKC and MAPKs-induced EGFR transactivation
✍ Scribed by Sang Hun Lee; Sun Im Na; Jung Sun Heo; Min Hee Kim; Yun Hee Kim; Min Young Lee; Seong Hong Kim; Yun Jung Lee; Ho Jae Han
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 404 KB
- Volume
- 106
- Category
- Article
- ISSN
- 0730-2312
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Reactive oxygen species (ROS) generated by a variety of endogenous factors and roles in embryonic stem (ES) cells has yet to be identified. Thus, we examined role of arachidonic acid (AA) in H~2~O~2~‐indued proliferation of mouse ES cells and its related signaling molecules. AA release was maximally increased in response to 10^−4^ M H~2~O~2~ for 1 h. In addition, H~2~O~2~ increased intracellular Ca^2+^ concentration ([Ca^2+^]~i~) and the phosphorylation of protein kinase C (PKC), p44/42, p38 mitogen‐activated protein kinase (MAPK), and JNK/SAPK. Moreover, H~2~O~2~ induced an increase in the phosphorylation of epidermal growth factor receptor (EGFR), which was blocked by the inhibition of p44/42 or p38 MAPKs. The inhibition of each signal molecule with specific inhibitors blocked H~2~O~2~‐induced cytosolic phospholipase A~2~ (cPLA~2~) activation and AA release. H~2~O~2~ increased NF‐κB phosphorylation to induce an increase in the levels of cyclooxygenase (COX)‐2 proteins. Subsequently, H~2~O~2~ stimulated PGE~2~ synthesis, which was reduced by the inhibition of NF‐κB activation. Moreover, each H~2~O~2~ or PGE~2~ increased DNA synthesis and the number of cells. However, H~2~O~2~‐induced increase in DNA synthesis was inhibited by the suppression of cPLA~2~ pathway. In conclusion, H~2~O~2~ increased AA release and PGE~2~ production by the upregulation of cPLA~2~ and COX‐2 via Ca^2+^/PKC/MAPKs and EGFR transactivation, subsequently proliferation of mouse ES cells. J. Cell. Biochem. 106: 787–797, 2009. © 2009 Wiley‐Liss, Inc.