In order to study whether tacrine and bis(7)-tacrine can prevent cell apoptosis induced by staurosporine in NG108-15 and HeLa cell lines. Phase-contrast and fluorescence microscopes were used to examine cell morphological changes. MTT assay was used to examine if staurosporine impairs cell metabolism. DNA was isolated and electrophoretically separated on 1% agarose gel to observe if there were DNA fragments. Western blot was made to analyse protein levels of anti-apoptotic Bcl-2 and proapoptotic Bax. The results showed that NG108-15 cells treated with 0.1 mol/L staurosporine for 12~24 h exhibited marked cell death and DNA fragmentation. Pre-treatment with 0.1 μmmol/L tacrine provided approximately 40% protective effect and resulted in obvious inhibition or delay DNA fragmentation. Moreover, NG108-15 cells treated with tacrine became elongated and polarized, and showed longer processes than control cells. Pretreatment with 0.1 mmol/L tacrine significantly increased the expression of Bcl-2 protein level and delayed the staurosporine-induced increase of Bax protein expression. However, bis(7)-tacrine did not show any protective effect on the cell impairment induced by staurosporine in NG108-15 cells. In HeLa cells 0.1 μmol/L staurosporine also induced significant cell injury, but pretreatment with tacrine and bis(7)-tacrine did not provide any obvious protective effect against this cell damage. These data suggest that tacrine markedly protect against apoptosis of NG108-15 cells but bis(7)-tacrine did not. Both tacrine and bis(7)-tacrine were not show to inhibit apoptosis of HeLa cells. It appears that the protective effects of tacrine against apoptosis not be mediated through AChE inhibition and has cell selective specifity.
PENG Fang-Fang, ZHANG Bai-Fang, ZHANG Jiang-Zhou, WU Dong-Cheng. Protective Effects of Tacrine and Bis(7)-Tacrine on Staurosporine-induced Apoptosis[J]. Progress in Biochemistry and Biophysics,2002,29(4):615-620
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