Exp Mol Med.  2011 Dec;43(12):653-659. 10.3858/emm.2011.43.12.074.

Hypoxia induces Wee1 expression and attenuates hydrogen peroxide-induced endothelial damage in MS1 cells

• Hong KS
• Kim HS
• Kim SH
• Lim DJ
• Park JY
• Kim SD

• KMID: 1058702
• DOI: http://doi.org/10.3858/emm.2011.43.12.074

Abstract

In an oxygen-depleted environment, endothelial cells initiate an adaptive pattern of synthesis, which may enable them to survive hypoxic crises. Using high-resolution two-dimensional gel electrophoresis in conjunction with mass spectroscopy, we obtained a 24 differential display of proteins in the pancreatic endothelial cell line, MS-1, at four time points following induction of hypoxia. The induction of Wee1 under hypoxia was confirmed both at the mRNA and protein levels. The phosphorylation of cell division cycle 2, which is downstream of Wee1, was also increased after hypoxic exposure. In addition, pre-exposure to hypoxia attenuated a decrease in hydrogen peroxide-induced cell number. The induction of bax (a pro-apoptotic protein) and reduction of bcl (an anti-apoptotic protein) after hypoxia stimulus were also attenuated by hypoxic pre-exposure. Moreover, hydrogen peroxide-induced morphologic damage did not appear in the wild-type Wee1-expressing cells. Taken together, our results suggest that Wee1 may have important role in hypoxia-induced pathophysiological situations in endothelial cells.

Keyword

cell hypoxia; endothelial cells; hydrogen peroxide; hypoxia inducible factor 1, alpha subunit; Wee1 protein, human

MeSH Terms

Animals
CDC2 Protein Kinase/metabolism
Cell Cycle Proteins/*genetics/metabolism
Cell Hypoxia
Cell Line
Cell Survival
Endothelial Cells/cytology/*metabolism
*Gene Expression Regulation
Hydrogen Peroxide/*metabolism
Mice
Nuclear Proteins/*genetics/metabolism
Pancreas/cytology
Phosphorylation
Protein-Tyrosine Kinases/*genetics/metabolism