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Activation of proteinkinase ERK mediates induction of macrophage MMP-12 by OxLDL

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Wuhan University Journal of Natural Sciences

Abstract

The present study was undertaken to investigate the effect of oxidized low density lipoprotein (oxLDL) on the expression of macrophage matrix metalloproteinase-12 (MMP-12), and the possible mechanisms. Activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was detected by Western blot Analysis. Enzymatic activity of MMP-12 was determined by β-casein zymography. RT-PCR analysis was used to measure the mRNA expression level of MMP-12. OxLDL-stimulated macrophages produced increased casein-degrading activities and oxLDL also significantly increased the mRNA level of MMP-12 in a dose-dependent manner. OxLDL stimulated the phosphorylation of ERK1/2 in macrophages. The use of the specific inhibitor indicated that the ERK1/2 signaling pathway was required for the induction of MMP-12. These data demonstrated that oxLDL induced MMP-12 expression in macrophages through an ERK1/2-dependent pathway.

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References

  1. Galis Z S, Sukhova G K, Lark M W,et al. Increased Expression of Matrix Metalloproteinases and Matrix Degrading Activity in Vulnerable Regions of Human Atherosclerotic Plaques.J Clin Invest, 1994,94: 2493–503.

    Article  Google Scholar 

  2. Belaaouaj A, Shipley J M, Kobayashi D K,et al. Human Macrophage Metalloelastase.The Journal of Biological Chemistry, 1995,270(24): 14568–14575.

    Article  Google Scholar 

  3. Matsumoto S, Kobayashi T, Katoh M,et al. Expression and Localization of Matrix Metalloproteinase-12 in the Aorta of Cholesterol-Fed Rabbits.American Journal of Pathology, 1998,153(1): 109–119.

    Google Scholar 

  4. Feinberg M W, Jain M K, Werner F,et al. Transforming Growth Factor-Beta 1 Inhibits Cytokine-Mediated Induction of Human Metalloelastase in Macrophages.J Biol Chem, 2000,275(33): 25766–73.

    Article  Google Scholar 

  5. Steinberg D, Lewis A. Conner Memorial Lecture—Oxidative Modification of LDL and Atherogenesis.Circulation, 1997,95: 1062–1071

    Google Scholar 

  6. Yang C M, Chiu C T, Wang C C,et al. Activation of Mitogen-Activated Protein Kinase by Oxidized Low-Density Lipoprotein in Canine Cultured Vascular Smooth Muscle Cells.Cell Signal, 2000,12(4): 205–14.

    Article  Google Scholar 

  7. Raza S L, Nehring L C, Shapiro S D,et al. Proteinase-Acti vated Receptor-1 Regulation of Macrophage Elastase (MMP-12) Secretion by Serine Proteinases.The Journal of Biological Chemistry, 2000,275(52): 41243–41250.

    Article  Google Scholar 

  8. Shapiro S D, Griffin G L, Gilbert D J,et al. Molecular Cloning, Chromosomal Localization, and Bacterial Expression of a Murine Macrophage Metalloelastase.The Journal of Biological Chemistry, 1992,267(7): 4664–4671.

    Google Scholar 

  9. Xu X P, Meisel S R, Ong J M,et al. Oxidized Low-Density Lipoprotein Regulates Matrix Metalloproteinase-9 and Its Tissue Inhibitor in Human Monocyte-Derived Macrophages.Circulation, 1999,99(8): 993–8.

    Google Scholar 

  10. Wu L, Tanimoto A, Murata Y,et al. Induction of Human Matrix Metalloproteinase-12 Gene Transcriptional Activity by GM-CSF Requires the AP-1 Binding Site in Human U937 Monocytic Cells.Biochem Biophys Res Commun, 2001,285 (2): 300–7.

    Article  Google Scholar 

  11. Ranganathan A C, Nelson K K, Rodriguez A M,et al. Manganese Superoxide Dismutase Signals Matrix Metalloproteinase Expressionvia H2O2-Dependent ERK1/2 Activation.The Journal of Biological Chemistry, 2001,276(17): 14264–14270.

    Google Scholar 

  12. Lai W C, Zhou M, Shankavaram U,et al. Differential Regulation of Lipopolysaccharide-Induced Monocyte Matrix Metalloproteinase (MMP)-1 and MMP-9 by p38 and Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinases.J Immunol, 2003,170(12): 6244–9.

    Google Scholar 

  13. Song L, Xu M, Lopes-Virella M F,et al. Quercetin Inhibits Matrix Metalloproteinase-1 Expression in Human Vascular Endothelial Cells through Extracellular Signal-Regulated Kinase.Arch Biochem Biophys, 2001,391(1): 72–8.

    Article  Google Scholar 

  14. Hamilton J A, Byrne R, Jessup W,et al. Comparison of Macrophages to Oxidized Low-Density Lipoprotein and Macrophage Colony-Stimulating Factor(M-CSF or CSF-1).Biochemistry Journal, 2001,354: 179–187.

    Article  Google Scholar 

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Correspondence to Zhou Xin.

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Foundation item: Supported by the Natural Science Foundation of Hubei Province (99J138)

Biography: He Chun-yan (1970-), female, Ph. D candidate, research direction: biochemistry diagnosis of atherosclerosis.

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Chun-yan, H., Xin, Z., Xiao-ming, L. et al. Activation of proteinkinase ERK mediates induction of macrophage MMP-12 by OxLDL. Wuhan Univ. J. Nat. Sci. 9, 120–124 (2004). https://doi.org/10.1007/BF02912732

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  • DOI: https://doi.org/10.1007/BF02912732

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