Homocysteine Impairs Endothelial Wound Healing by Activating Metabotropic Glutamate Receptor 5

作者: CHENG-HUNG CHEN , RICHARD S. BEARD , SHAWN E. BEARDEN

DOI: 10.1111/J.1549-8719.2012.00159.X

关键词: ImmunologyAngiogenesisSmall hairpin RNAPharmacologyProtein kinase CWound healingBiologyCell growthAgonistHomocysteineMetabotropic glutamate receptor 5

摘要: Please cite this paper as: Chen C-H, Beard RS, Bearden SE. Homocysteine impairs endothelial wound healing by activating metabotropic glutamate receptor 5. Microcirculation 19: 285–295, 2012. Abstract Objective:  Hcy is an independent risk factor for cerebrovascular disease and cognitive impairment. The purpose of study was to elucidate the role mGluR5 in Hcy-mediated impairment cerebral repair. Methods:  Mouse CMVECs (bEnd.3) were used conjunction with directed pharmacology shRNA. AutoDock simulate docking ligand–receptor interactions. Results:  (20 μM) significantly increased Cx43-pS368 mGluR5- PKC-dependent mechanisms. attenuated repair mGluR5-dependent mechanism over six-day period but did not alter cell proliferation a assay, suggesting that attenuation may be due dysfunctional migration HHcy. expression Cx43 at edge mGluR5. Direct activation mGluR5, using specific agonist CHPG, sufficient reproduce results whereas KO shRNA, or inhibition MPEP, blocked response Hcy. Conclusions:  Inhibition could novel strategy promoting patients Activation viable disrupting angiogenesis.

参考文章(41)
Hong Wang, XiaoHua Jiang, Fan Yang, Gary B Chapman, William Durante, Nicholas ES Sibinga, Andrew I Schafer, None, Cyclin A transcriptional suppression is the major mechanism mediating homocysteine-induced endothelial cell growth inhibition. Blood. ,vol. 99, pp. 939- 945 ,(2002) , 10.1182/BLOOD.V99.3.939
Naoki Kunishima, Yoshimi Shimada, Yuji Tsuji, Toshihiro Sato, Masaki Yamamoto, Takashi Kumasaka, Shigetada Nakanishi, Hisato Jingami, Kosuke Morikawa, Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor Nature. ,vol. 407, pp. 971- 977 ,(2000) , 10.1038/35039564
Md S. Jamaluddin, Irene Chen, Fan Yang, Xiaohua Jiang, Michael Jan, Xiaoming Liu, Andrew I. Schafer, William Durante, Xiaofeng Yang, Hong Wang, Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene Blood. ,vol. 110, pp. 3648- 3655 ,(2007) , 10.1182/BLOOD-2007-06-096701
Cindy Qiu, Petula Coutinho, Stefanie Frank, Susanne Franke, Lee-yong Law, Paul Martin, Colin R. Green, David L. Becker, Targeting Connexin43 Expression Accelerates the Rate of Wound Repair Current Biology. ,vol. 13, pp. 1697- 1703 ,(2003) , 10.1016/J.CUB.2003.09.007
Jamie N Mayo, Richard S Beard, Tulin O Price, Cheng-Hung Chen, Michelle A Erickson, Nuran Ercal, William A Banks, Shawn E Bearden, Nitrative Stress in Cerebral Endothelium is Mediated by mGluR5 in Hyperhomocysteinemia Journal of Cerebral Blood Flow and Metabolism. ,vol. 32, pp. 825- 834 ,(2012) , 10.1038/JCBFM.2011.185
Sheng-You Huang, Xiaoqin Zou, Advances and Challenges in Protein-Ligand Docking International Journal of Molecular Sciences. ,vol. 11, pp. 3016- 3034 ,(2010) , 10.3390/IJMS11083016
Stephan Olk, Andrey Turchinovich, Michael Grzendowski, Kai Stühler, Helmut E. Meyer, Georg Zoidl, Rolf Dermietzel, Proteomic analysis of astroglial connexin43 silencing uncovers a cytoskeletal platform involved in process formation and migration Glia. ,vol. 58, pp. 494- 505 ,(2009) , 10.1002/GLIA.20942
Joell L. Solan, Paul D. Lampe, Connexin43 phosphorylation: structural changes and biological effects. Biochemical Journal. ,vol. 419, pp. 261- 272 ,(2009) , 10.1042/BJ20082319
Antonio De Blasi, Peter Jeffrey Conn, Jean-Philippe Pin, Ferdinando Nicoletti, Molecular determinants of metabotropic glutamate receptor signaling Trends in Pharmacological Sciences. ,vol. 22, pp. 114- 120 ,(2001) , 10.1016/S0165-6147(00)01635-7
F. Nicoletti, J. Bockaert, G.L. Collingridge, P.J. Conn, F. Ferraguti, D.D. Schoepp, J.T. Wroblewski, J.P. Pin, Metabotropic glutamate receptors: From the workbench to the bedside Neuropharmacology. ,vol. 60, pp. 1017- 1041 ,(2011) , 10.1016/J.NEUROPHARM.2010.10.022