Effects of magnesium on matrix metalloproteinase-2 production in cultured rat cardiac fibroblasts.
The precise correlation between magnesium and cardiac disease remains to be established. Matrix metalloproteinases (MMPs) are important in cardiac disease such as heart failure. Cardiac fibroblasts are the most abundant cell type in the heart and play an important role in the regulation of collagen degradation by MMPs. To assess the association between magnesium and MMPs, we examined the effects of different extracellular magnesium concentrations (0-3.0 mmol/L) on MMP-2 production in cultured rat cardiac fibroblasts. Using gelatin zymography and western blotting, we found that magnesium reduced MMP-2 production dose-dependently, and this effect was inhibited by the tyrosine kinase inhibitors, genistein or herbimycin A. The results of this study indicated that the beneficial effect of magnesium supplementation on the cardiac disease may be due, at least in part, to the inhibitory effect of magnesium on production of MMPs in cardiac fibroblasts, which appears to be mediated by a protein tyrosine phosphorylation related signal transduction pathway.
Yue
Hong
H
First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka-Cho Fukui 910-1193, Japan.
Uzui
Hiroyasu
H
Lee
Jong-Dae
JD
Shimizu
Hiromasa
H
Ueda
Takanori
T
D000818:Animals; D016227:Benzoquinones; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology*; D019833:Genistein / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects*
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2; D008274:Magnesium