Stimulation effect of microcystin-LR on matrix metalloproteinase-2/-9 expression in mouse liver.

ABSTRACT

In order to investigate the potential effects of microcystin-LR (MC-LR) on the expression of metalloproteinases (MMPs), Mice were orally administered with MC-LR in drinking water (0, 1, 40 and 80 µg/L) for 180 d, and hepatic MMP-2/-9 expression was evaluated at the levels of enzyme activity, protein level and mRNA expression. Histopathologic observation showed the obvious hepatic lymphocyte infiltration and fatty degeneration in the mice exposed to 40 and 80 µg/L MC-LR. Immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) revealed that excess MMP-2/-9 proteins were produced in livers of the mice exposed to MC-LR at the higher concentrations. Hepatic MMP-9 level was elevated from 0.6 ng/g liver weight in control to 1.4 ng/g liver weight in 80-µg/L group, but a slight increase was found for MMP-2 level. Real time PCR showed that MMP-2/-9 mRNA expression was up-regulated by 6.9 fold and 5.0 fold after 80-µg/L-MC treatment, respectively. MMP-2/-9 expression showed a good dose-dependent manner at both protein and mRNA levels. ELISA demonstrated that MC-LR stimulated phosphorylation of mitogen-activated protein kinases, a potential signal transduction pathway of the MMP-2/-9 expression alteration. This study revealed a significant alteration in hepatic MMP-2/-9 expression induced by MC-LR, which might be involved in cell invasion and metastasis.