HCMV infection attenuates hydrogen peroxide induced endothelial apoptosis-- involvement of ERK pathway.
Human cytomegalovirus (HCMV) exerts anti-apoptotic effect during early stage of infection, which provides HCMV time for propagation. We investigated pathways mediating the resistance to H(2)O(2)-induced cell death - a self-defense mechanism to remove infected cells. We found that human aortic endothelial cells (HAECs) infected with VHL/E strain of HCMV during first 3 days were resistant to H(2)O(2) (0-2 mM) induced apoptosis. This anti-apoptotic effect may be mediated by the upregulation of Bcl-2, an anti-apoptotic protein through the activation pro-survival pathway extracellular signal regulated kinase (ERK). Through this mechanism, HCMV is able to propagate and causes endothelial dysfunction, hence vascular disease.
Wang
Jing
J
Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Adult Cardiac Services, Texas Heart Institute, St. Luke's Episcopal Hospital, Baylor College of Medicine, MS NAB 2010, One Baylor Plaza, Houston, TX 77030, USA.
Shen
Ying H
YH
Utama
Budi
B
Wang
Jian
J
LeMaire
Scott A
SA
Coselli
Joseph S
JS
Vercellotti
Greg M
GM
Wang
Xing Li
XL
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000821:virology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases