간암세포에서 MMPs의 S-nitrosylation에 의한 활성촉진

초록

This study aimed to determine whether treatment of NO donors affects expression and activity of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in liver cancer cells that have differential gelatinase MMP activities. In HepG2 cell line showing the MMP-2 activity primarily, the expressions of MMP-2 mRNA and protein were increased by low concentration (<~50mM of SNP and SNAP) of NO-donors, but decreased by high concetration (>50mM). However, expression levels of TIMP-1 were increased even at high concentration of NO-donors without change of mRNA expression. Interestingly, DTT treated to assess the NO-mediated S-nitosylation of both MMP-2 and TIMP-1 inhibited completely the expression of MMP-2 and TIMP-1. In Hepa 1C1C-7 cell line also, the gelatinase activities of both MMP-2 and MMP-9 were increased by NO-donor as shown in HepG2 cells, but delayed or decreased dose dependently by DTT treatment. In SK-Hep-1 cell lines that has high gelatinase activities of both MMP-2 and ? also, NO increased their activities and protein expressions. Thus, gelatin zymography revealed an increase both in the expression and activities of MMP-2 and/or after exposure to the NO.