Effect of 17β estradiol on statin‐induced apoptosis (1102.38)

Abstract

We have previously studied the effects of estrogen (E) on statin‐induced myotoxicity with E providing no apparent protection. In our studies E was added simultaneously with the statins, possibly explaining the lack of E effect. The anti‐apoptotic effect of E has been shown to be tightly linked to induction of hsp27. The purpose of this study was to establish the dependence of an anti‐apoptotic effect on prior E exposure. C2C12 cells were cultured in growth media (GM) and plated in 6‐well plates. After plates reached approximately 70% confluence, cells were exposed to one of six treatments: control (GM), E (10‐8 M 17β Estradiol), SS (10‐4 M Simvastatin), or three different treatments of E + SS (no E pretreatment; 45 min E pretreatment; or 45 minute E pretreatment with continued E+SS). After 24‐48 hours exposure, cells were DAPI‐stained and apoptotic nuclei were quantified. Data was analyzed by 1‐way ANOVA; p<0.05. As in previous studies, SS induced apoptosis with a significant increase in condensed nuclei (33.8% +/‐ 11.7% vs 6.2% +/‐ 2.6% in GM). Addition of E had no effect under any of the three E+SS conditions (45.4% +/‐ 15.6%, 34.9% +/‐ 14.5%, 35.5% +/‐ 15.4%). These results further support our earlier findings that question the ability of E to protect against statin‐induced toxicity. Pre‐treatment with E, known to induce hsp27, had no impact on the response to SS. Further studies are needed to explain the discrepancy between these data and E effects in other models of apoptosis.Grant Funding Source: NSF STEP Grant