Regulation of matrix metalloproteinase-9 and tissue plasminogen activator activity by alpha-synuclein in rat primary glial cells.
It is increasingly evident that neuroinflammatory response is involved in the pathogenesis of Parkinson's disease. In this study, we examined whether alpha-synuclein, a major components of Lewy body that has been implicated in the modulation of neuroinflammation, regulates MMP-9 and tPA activity, which plays important roles in neurodegeneration as well as regeneration processes, in cultured rat primary glial cells. Monomeric alpha-synuclein dose-dependently increased MMP-9 but not MMP-2 activity as well as mRNA level from cultured rat primary astrocytes and microglial cells. Maximal stimulation was observed at 50 nM alpha-synuclein. In contrast, the activity of tPA was decreased by alpha-synuclein with only marginal changes in the level of mRNA encoding tPA, if any. Interestingly, same concentration of alpha-synuclein aggregates did not induce MMP-9 activity. Overexpression of alpha-synuclein in rat primary astrocytes similarly increased MMP-9 activity. Treatment of alpha-synuclein increased the phosphorylation of ERK1/2 and the inhibition of ERK1/2 reversed the changes in MMP-9 and tPA activity. These results suggest further functional role of alpha-synuclein via regulation of protease systems through modulation of ERK1/2 activity in brain.
Joo
So Hyun
SH
Department of Pharmacology, Institute of Biomedical Sciences and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Kwon
Kyoung Ja
KJ
Kim
Ji Woon
JW
Kim
Joo Wan
JW
Hasan
Mohammad Rakibul
MR
Lee
He-Jin
HJ
Han
Seol-Heui
SH
Shin
Chan Young
CY
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005625:Frontal Lobe / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D012333:RNA, Messenger; D051844:alpha-Synuclein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D010959:Tissue Plasminogen Activator; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9