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Endogenous agmatine inhibits cerebral vascular matrix metalloproteinases expression by regulating activating transcription factor 3 and endothelial nitric oxide synthesis

 Hyun Joo Jung  ;  Mei Zi Yang  ;  Ki Hyo Kwon  ;  Midori A. Yenari  ;  Yoon Jung Choi  ;  Won Taek Lee  ;  Kyung Ah Park  ;  Jong Eun Lee 
 CURRENT NEUROVASCULAR RESEARCH, Vol.7(3) : 201-212, 2010 
Journal Title
Issue Date
Activating Transcription Factor 3/genetics ; Activating Transcription Factor 3/metabolism* ; Agmatine/metabolism* ; Analysis of Variance ; Animals ; Blotting, Western ; Brain/blood supply ; Brain/metabolism* ; Cell Line ; Cells, Cultured ; Chromatography, High Pressure Liquid ; Endothelium, Vascular/metabolism* ; Immunohistochemistry ; Matrix Metalloproteinases/genetics ; Matrix Metalloproteinases/metabolism* ; Mice ; Nitric Oxide/biosynthesis* ; Nitric Oxide/genetics ; Nitric Oxide Synthase Type III/genetics ; Nitric Oxide Synthase Type III/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
Arginine decarboxylase ; agmatine ; activating transcription factor 3 ; endothelial cell ; matrix metalloproteinases ; endothelial nitric oxide synthase
Earlier investigations from our laboratory demonstrated that the expression of matrix metalloproteinases (MMPs) was down-regulated by exogenously administered agmatine against ischemia-like injuries in the murine brain capillary endothelial (bEnd.3) cells. In our present study, we intended to investigate the mechanism involved in the inhibition of MMPs in bEnd.3 cells infected with retroviral containing human arginine decarboxylase (hADC) gene which can synthesize agmatine endogenously (ADCDeltabEnd.3 cells). The ADCDeltabEnd.3 cells were subjected to oxygen glucose deprivation (OGD, 6 hrs) with reperfusion (18 hrs). High performance liquid chromatography (HPLC) analysis revealed the high levels of agmatine in the ADCDeltabEnd.3 cells compared to other experimental groups. The results demonstrated significant decrease in cell death and increase in the nitric oxide (NO) production in the ADCDeltabEnd.3 cells. The increased expression of MMP-2 and MMP-9, and decreased expression of endothelial nitric oxide synthase (eNOS) by ischemic injury was attenuated in ADCDeltabEnd.3 cells. Moreover, the expression of activating transcription factor 3 (ATF3) was increased significantly in ADCDeltabEnd.3 cells. In addition, the suppression of the MMP-2 and MMP-9 expression in ADCDeltabEnd.3 cells was prevented with ATF3 small interfering RNA (siRNA) treatment. These results suggest that the endogenous agmatine in ADCDeltabEnd.3 cells inhibits the MMPs expression mediated via the regulation of eNOS, NO and ATF3.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyung Ah(박경아)
Lee, Won Taek(이원택) ORCID logo https://orcid.org/0000-0001-7348-9562
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Chung, Huyun Joo(정현주)
Choi, Yoon Jung(최윤정)
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