The regulation of agmatine on MMP expression in the cerebral endothelial cells overexpressed ADC gene  

作　　者：YANG Mei-zi1,JIN Yong-jun2,ZHANG Shu-ping1(1.Department of Pharmacology,Bin Zhou Medical University,Yantai 264003,China 2.Department of Endocrinology,Affiliated Hospital of Binzhou Medical University,Binzhou 256603,China) 

出　　处：《沈阳药科大学学报》2008年第S1期58-59,共2页Journal of Shenyang Pharmaceutical University

摘　　要：Objective In this study we will investigate the effect and possible mechanism of agmatine on MMP expression.Methods We established a transfection of human ADC gene into the murine bEnd.3 cells(bEnd.3-ADC)by the retroviral packaging cell line PT67.The bEnd.3-ADC cells were maintained in the hypoxia chamber for 6 hours,then returned to a normoxic incubator with glucose for 16 hours.We performed RT-PCR and western blot analysis against MMP-2,MMP-9,eNOS and ATF3,and measured the production of NO using Griess reagent.To determine the possible mechanism of agmatine on MMP expression we used inhibitory study.Results The expression of MMP was decreased by agmatine administered exogenously and endogenously,while eNOS was increased.We showed L-NAME(NOS inhibitor)altered the suppression of MMP-9 by exogenously administered agmatine.It seems that MMP-9 suppression by exogenously administrated agmatine is mediated,at least in part,via eNOS.We also found that ATF3 was increased significantly in ADC overexpression cells,but it was attenuated by NOS inhibitor.Furthermore,we found the suppression of MMP by agmatine was attenuated in cells transfected with ATF3 siRNA.Conclusions Our study suggested that endogenously administered agmatine suppress the MMP-2 and MMP-9 expression via eNOS-ATF3-MMPs pathway.Objective In this study we will investigate the effect and possible mechanism of agmatine on MMP expression.Methods We established a transfection of human ADC gene into the murine bEnd.3 cells(bEnd.3-ADC)by the retroviral packaging cell line PT67.The bEnd.3-ADC cells were maintained in the hypoxia chamber for 6 hours,then returned to a normoxic incubator with glucose for 16 hours.We performed RT-PCR and western blot analysis against MMP-2,MMP-9,eNOS and ATF3,and measured the production of NO using Griess reagent.To determine the possible mechanism of agmatine on MMP expression we used inhibitory study.Results The expression of MMP was decreased by agmatine administered exogenously and endogenously,while eNOS was increased.We showed L-NAME(NOS inhibitor)altered the suppression of MMP-9 by exogenously administered agmatine.It seems that MMP-9 suppression by exogenously administrated agmatine is mediated,at least in part,via eNOS.We also found that ATF3 was increased significantly in ADC overexpression cells,but it was attenuated by NOS inhibitor.Furthermore,we found the suppression of MMP by agmatine was attenuated in cells transfected with ATF3 siRNA.Conclusions Our study suggested that endogenously administered agmatine suppress the MMP-2 and MMP-9 expression via eNOS-ATF3-MMPs pathway.

关 键 词：MMP ADC gene ENOS ATF3 

分 类 号：R96[医药卫生—药理学]