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Hypoxia induces Wee1 expression and attenuates hydrogen peroxide-induced endothelial damage in MS1 cells
Authors:Hong Ki Sun  Kim Hyeon Soo  Kim Se Hoon  Lim Dong Jun  Park Jung Yul  Kim Sang Dae
Institution:Department of Neurosurgery Korea University Ansan Hospital Korea University College of Medicine Ansan 425-707, Korea.
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.
Keywords:cell hypoxia  endothelial cells  hydrogen peroxide  hypoxia inducible factor 1  α subunit  Wee1 protein  human
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