Antioxidative action of N-a-tosyl-L-lysine chloromethyl ketone prevents death of glutathione-depleted cardiomyocytes induced by hydrogen peroxide英文文献资料.docVIP

Vol.1, No.3, 164-171 (2010) Journal of Biophysical Chemistry doi:10.4236/jbpc.2010.13019 Antioxidative action of N-?-tosyl-L-lysine chloromethyl ketone prevents death of glutathione-depleted cardiomyocytes induced by hydrogen peroxide Kiyoshi Takahashi, Kyohei Oyama, Hironori Motoshige, Koichi Sakurai* Division of Biochemistry, Department of Life science, Hokkaido Pharmaceutical University School of Pharmacy, Katsuraoka-cho, Otaru, Hokkaido, Japan; *Corresponding Author: ks51@hokuyakudai.ac.jp Received 20 August 2010; revised 22 September 2010; accepted 25 September 2010. ABSTRACT 1. INTRODUCTION Hydrogen peroxide (H2O2) induces the hyper- trophy in cultured H9c2 cardiomyocytes and cell death in glutathione (GSH)-depleted H9c2 cells. In the present study, we observed that pretreatment with a serine protease inhibitor, N-?-tosyl-L-lysine chloromethyl ketone (TLCK), significantly prevented the H2O2-induced cell damages in GSH-depleted H9c2 cells in a con- centration-dependent manner. The phase con- trast microscopy revealed that although the exposure of the GSH-depleted H9c2 cells to H2O2 resulted in a globular shape of the cells, TLCK prevented the occurrence of H2O2-in- duced morphological changes. TLCK also in- hibited the generation of reactive oxygen spe- cies in the cells after addition of H2O2, sug- gesting that the antioxidant action of TLCK is involved in the protection against the cell dam- ages by H2O2. Application of TLCK after ~30 min of exposure to H2O2 could significantly protect the cells from cell damages. The other serine protease inhibitors that were tested could not prevent the cell damages in GSH- depleted H9c2 cells. Pretreatment with an in- hibitor of nuclear factor-?? translocation into the nucleus and a proteasome inhibitor did not prevent the cell damages in GSH-depleted H9c2 cells.