Peroxynitrite-mediated matrix metalloproteinase-2 activation in human hepatic stellate cells.
To investigate whether hepatic stellate cells (HSCs) alter their expression of MMPs after exposure to nitrogen oxide intermediate (NOI), a human hepatic stellate cell line, LI90 cells, was stimulated with an NO donor, SNAP, or a peroxynitrite donor, SIN-1, and the culture supernatants were analyzed by gelatin zymography or anti-MMPs immunoblot. Although SIN-1 did not enhance the secretions of MMP-1 and 13, SIN-1 induced the NF-kappaB activation, MT1-MMP expression and the secretion of activated MMP-2 in LI90 cells. These results suggest that peroxynitrite may contribute to the remodeling of the extracellular matrix in liver by activating pro-MMP-2.
Migita
Kiyoshi
K
Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura 856-8562, Japan. migita@nmc.hosp.go.jp
Maeda
Yumi
Y
Abiru
Seigo
S
Komori
Atsumasa
A
Yokoyama
Terufumi
T
Takii
Yasushi
Y
Nakamura
Minoru
M
Yatsuhashi
Hiroshi
H
Eguchi
Katsumi
K
Ishibashi
Hiromi
H
D002460:Cell Line; D017364:Collagenases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009566:Nitrates; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D019715:Tissue Inhibitor of Metalloproteinase-1; D000072000:NF-KappaB Inhibitor alpha; D030421:Peroxynitrous Acid; C002385:linsidomine; D008981:Molsidomine; D020928:Mitogen-Activated Protein Kinases; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D010396:Penicillamine