The Effects of Arsenic Trioxide on Acetylation of Histone H3 of Splenic Lymphocytes in MRL/lpr Mice

Abstract: This study aimed to investigate the effects of arsenic trioxide (ATO) on the acetylation status of the histone H3 of splenic lymphocytes from MRL/lpr mice and the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Spleens were isolated from MRL/lpr mice and C57BL/6J mice at 20 weeks of age under specific pathogen-free condition and made to suspensions. Splenic lymphocytes were stimulated in vitro for 48 h in the presence of PHA-p (20 μg/ml) and IL-2(1 000 U/ml)， then were divided randomly into 3 groups: ATO group (treated with 1.0 μmol/L ATO for 24 h)， TSA group (treated with 300 ng/ml TSA for 24 h) and RPMI 1640 group (treated with RPMI 1640 for 24 h). Expression levels of acetylated histones H3 in 20-week-old MRL/lpr splenocytes were detected by Western blot. The activities of HDAC and HAT were evaluated via the corresponding activity assay kits. The results showed that in MRL/lpr mice， the degrees of acetylated histone H3 in RPMI 1640 group， ATO group and TSA group were 0.46±0.06， 0.87±0.02 and 1.6±0.13， respectively. And the difference was statistically significant (P<0.01). Compared with RPMI 1640 group， ATO group and TSA group could significantly reduce the activity of HDAC (P<0.01). However， for the HAT activity， no significant difference was observed between ATO group as well as between TSA group versus RPMI 1640 group. HDAC/HAT ratios in ATO group as well as TSA group were lower than RPMI 1640 group. There was no difference between ATO group and RPMI 1640 group in C57BL/6J mice (P<0.05). It was concluded that ATO can inhibit the activity of HDAC， lower the ratio of HDAC/HAT， and improve the acetylation level of histone H3 in the MRL/lpr splenic lymphocytes， and it was of no effect in normal mice.

CSTR: 32200.14.cjcb.2010.05.0011