title: Pretreatment with pPolyHb attenuates H2O2-induced endothelial cell injury through inhibition of JNK/p38 MAPK pathway by upregulation of heme oxygenase-1.
abstract: Polymerized porcine hemoglobin (pPolyHb) exhibits a protective effect on ischemia/reperfusion of organ grafts. A series of experiments were performed to explore the underlying cytoprotective mechanisms of pPolyHb pretreatment on H2O2-induced cell death and apoptosis. The results showed that the pretreatment augmented heme oxygenase-1 (HO-1) expression, and at the same time, decreased the phosphorylation of JNK/p38 mitogen-activated protein kinase (MAPK) and intracellular ROS generation in H2O2-treated HUVECs. Moreover, the inhibition of HO-1 expression by tin porphyrin (SnPP) abolished the protective effects of pPolyHb, which suggested that the cytoprotective effect of pPolyHb involves upregulating HO-1 and subsequently decreasing the phosphorylation of the JNK and p38 MAPK and ROS generation.
authors.affiliation: College of Life Science, Northwest University , Xi'an , P. R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xue
authors.forename: Kunping
authors.initials: K
authors.lastname: Yan
authors.forename: Xiufang
authors.initials: X
authors.lastname: Zhao
authors.forename: Wenjin
authors.initials: W
authors.lastname: Zhu
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.forename: Zhilan
authors.initials: Z
authors.lastname: Xie
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhu
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
mesh_terms: D004730:Endothelium, Vascular / Q000201:enzymology / Q000293:injuries; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006454:Hemoglobins / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; C037158:polyhemoglobin; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: JNK/p38 MAPK; heme oxygenase-1; human umbilical vein endothelial cells; hydrogen peroxide; polymerized porcine hemoglobin