Agmatine inhibits matrix metalloproteinase-9 via endothelial nitric oxide synthase in cerebral endothelial cells

Zi Yang Mei, Chin Mun Chin, Jung Choi Yoon, Ja-Hyun Baik, Ah Park Kyung, Taek Lee Won, Eun Lee Jong

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objectives: Matrix metalloproteinases (MMPs) are up-regulated by ischemic injury and degrade the basement membrane of brain vessels to promote cell death and tissue injury. We previously showed that agmatine has a neuroprotective effect on neurons against ischemic injury. In the present study, we investigated the effect of agmatine on the expression of MMPs and nitric oxide (NO) production in cerebral endothelial cells (CECs) after oxygen-glucose deprivation (OGD)-reperfusion injury and its potential association with endothelial nitric oxide synthase (eNOS). Methods: Primary cultured endothelial cells from murine brain and bEnd.3 cells were subjected to OGD-reperfusion injury. Protein and mRNA levels of both MMP-2 and MMP-9 were determined by immunocytochemical analysis, Western blot and RT-PCR. Protein levels of eNOS were evaluated by Western blot in the CECs. The production of NO was measured using the Griess reagent. Results: Agmatine attenuated the expression of MMP-2 and MMP-9 induced by ischemic injury at the protein and mRNA level, while agmatine increased the expression of eNOS directly. NO production was decreased in CECs after similar insult and was increased by agmatine treatment. In the presence of a nitric oxide synthase (NOS) inhibitor, N ω-nitro-L-arginine methyl ester (L-NAME), the expression levels of MMP-2 were decreased, but the expression of MMP-9 was not decreased by agmatine administration. However, NO production was suppressed by a non-specific NOS inhibitor in the agmatine treatment group. Conclusion: Our study supports that the down-regulation of MMP-9 by agmatine runs parallel to the up-regulation of eNOS and the maintenance of functional NO release.

Original languageEnglish
Pages (from-to)749-754
Number of pages6
JournalNeurological Research
Volume29
Issue number7
DOIs
Publication statusPublished - 2007 Oct 1

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Agmatine
Nitric Oxide Synthase Type III
Matrix Metalloproteinase 9
Endothelial Cells
Nitric Oxide
Matrix Metalloproteinase 2
Wounds and Injuries
Reperfusion Injury
Matrix Metalloproteinases
Nitric Oxide Synthase
Western Blotting
Oxygen
Glucose
Messenger RNA
Proteins
NG-Nitroarginine Methyl Ester
Brain
Neuroprotective Agents
Basement Membrane
Cultured Cells

Keywords

  • Agmatine
  • Endothelial cell
  • eNOS
  • MMPs
  • NO

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Agmatine inhibits matrix metalloproteinase-9 via endothelial nitric oxide synthase in cerebral endothelial cells. / Mei, Zi Yang; Chin, Chin Mun; Yoon, Jung Choi; Baik, Ja-Hyun; Kyung, Ah Park; Won, Taek Lee; Jong, Eun Lee.

In: Neurological Research, Vol. 29, No. 7, 01.10.2007, p. 749-754.

Research output: Contribution to journalArticle

Mei, Zi Yang ; Chin, Chin Mun ; Yoon, Jung Choi ; Baik, Ja-Hyun ; Kyung, Ah Park ; Won, Taek Lee ; Jong, Eun Lee. / Agmatine inhibits matrix metalloproteinase-9 via endothelial nitric oxide synthase in cerebral endothelial cells. In: Neurological Research. 2007 ; Vol. 29, No. 7. pp. 749-754.
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AU - Chin, Chin Mun

AU - Yoon, Jung Choi

AU - Baik, Ja-Hyun

AU - Kyung, Ah Park

AU - Won, Taek Lee

AU - Jong, Eun Lee

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N2 - Objectives: Matrix metalloproteinases (MMPs) are up-regulated by ischemic injury and degrade the basement membrane of brain vessels to promote cell death and tissue injury. We previously showed that agmatine has a neuroprotective effect on neurons against ischemic injury. In the present study, we investigated the effect of agmatine on the expression of MMPs and nitric oxide (NO) production in cerebral endothelial cells (CECs) after oxygen-glucose deprivation (OGD)-reperfusion injury and its potential association with endothelial nitric oxide synthase (eNOS). Methods: Primary cultured endothelial cells from murine brain and bEnd.3 cells were subjected to OGD-reperfusion injury. Protein and mRNA levels of both MMP-2 and MMP-9 were determined by immunocytochemical analysis, Western blot and RT-PCR. Protein levels of eNOS were evaluated by Western blot in the CECs. The production of NO was measured using the Griess reagent. Results: Agmatine attenuated the expression of MMP-2 and MMP-9 induced by ischemic injury at the protein and mRNA level, while agmatine increased the expression of eNOS directly. NO production was decreased in CECs after similar insult and was increased by agmatine treatment. In the presence of a nitric oxide synthase (NOS) inhibitor, N ω-nitro-L-arginine methyl ester (L-NAME), the expression levels of MMP-2 were decreased, but the expression of MMP-9 was not decreased by agmatine administration. However, NO production was suppressed by a non-specific NOS inhibitor in the agmatine treatment group. Conclusion: Our study supports that the down-regulation of MMP-9 by agmatine runs parallel to the up-regulation of eNOS and the maintenance of functional NO release.

AB - Objectives: Matrix metalloproteinases (MMPs) are up-regulated by ischemic injury and degrade the basement membrane of brain vessels to promote cell death and tissue injury. We previously showed that agmatine has a neuroprotective effect on neurons against ischemic injury. In the present study, we investigated the effect of agmatine on the expression of MMPs and nitric oxide (NO) production in cerebral endothelial cells (CECs) after oxygen-glucose deprivation (OGD)-reperfusion injury and its potential association with endothelial nitric oxide synthase (eNOS). Methods: Primary cultured endothelial cells from murine brain and bEnd.3 cells were subjected to OGD-reperfusion injury. Protein and mRNA levels of both MMP-2 and MMP-9 were determined by immunocytochemical analysis, Western blot and RT-PCR. Protein levels of eNOS were evaluated by Western blot in the CECs. The production of NO was measured using the Griess reagent. Results: Agmatine attenuated the expression of MMP-2 and MMP-9 induced by ischemic injury at the protein and mRNA level, while agmatine increased the expression of eNOS directly. NO production was decreased in CECs after similar insult and was increased by agmatine treatment. In the presence of a nitric oxide synthase (NOS) inhibitor, N ω-nitro-L-arginine methyl ester (L-NAME), the expression levels of MMP-2 were decreased, but the expression of MMP-9 was not decreased by agmatine administration. However, NO production was suppressed by a non-specific NOS inhibitor in the agmatine treatment group. Conclusion: Our study supports that the down-regulation of MMP-9 by agmatine runs parallel to the up-regulation of eNOS and the maintenance of functional NO release.

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