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High glucose increase cell cycle regulatory proteins level of mouse embryonic stem cells via PI3‐K/Akt and MAPKs signal pathways
Author(s) -
Kim Yun Hee,
Heo Jung Sun,
Han Ho Jae
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20706
Subject(s) - protein kinase b , cyclin dependent kinase , cell cycle , kinase , microbiology and biotechnology , biology , cell growth , cyclin e , signal transduction , chemistry , protein kinase a , cyclin dependent kinase 2 , biochemistry , cell
This study examined the effects of high glucose on cell proliferation and its related signal pathways using mouse embryonic stem (ES) cells. Here, we showed that high glucose level significantly increased [ 3 H]thymidine incorporation, BrdU incorporation, the number of cells, [ 3 H]leucine, and [ 3 H]proline incorporation in a time‐(>3 hr) and dose‐(>25 mM) dependent manner. Moreover, high glucose level increased the cellular reactive oxygen species (ROS), Akt, and mitogen‐activated protein kinases (MAPKs) phosphorylation. Subsequently, these signaling molecules involved in high glucose‐induced increase of [ 3 H]thymidine incorporation. High glucose level also increased cyclin D1, cyclin E, cyclin‐dependent kinase (CDK) 2, and CDK 4 protein levels, which is cell cycle regulatory proteins acting in G1–S phase of cell cycle. Inhibition of phosphatidylinositol 3‐kinase (PI3‐K) (LY 294002: PI3‐kinase inhibitor, 10 −6 M), Akt (Akt inhibitor, 10 −5 M), and p44/42 MAPKs (PD 98059: MEK inhibitor, 10 −5 M) decreased these proteins. High glucose level phosphorylated the RB protein, which was decreased by inhibition of PI3‐K and Akt. In conclusion, high glucose level stimulates mouse ES cell proliferation via the PI3‐K/Akt and MAPKs pathways. J. Cell. Physiol. 209: 94–102, 2006. © 2006 Wiley‐Liss, Inc.