The role of extracellular signal-regulated kinase in induction of apoptosis with salvia miltiorrhiza monomer IH764-3 in hepatic stellate cells.
- Author:
Shu-Ming FANG
1
;
Chun-Sheng LI
;
Jun-Yan AN
;
Zhi-Na DUN
;
Dong-Mei YAO
;
Lei LIU
;
Xiao-Lan ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; physiology; Cell Line; Down-Regulation; drug effects; Drugs, Chinese Herbal; isolation & purification; pharmacology; Hepatic Stellate Cells; cytology; Humans; Hydrogen Peroxide; pharmacology; Mitogen-Activated Protein Kinase 3; genetics; metabolism; RNA, Messenger; genetics; metabolism; Salvia miltiorrhiza; chemistry
- From: Chinese Journal of Applied Physiology 2011;27(4):402-406
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect of Salvia miltiorrhiza monomer IH764-3 on apoptosis in hydrogen peroxide (H2O2)-stimulated hepatic stellate cells (HSCs).
METHODSHSCs were cultured in medium with different IH764-3 doses (10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L) and without IH764-3. Direct cell count, 3H-thymidine incorporation, Annexin-V/Propidium Iodide double-labeled flow cytometry, TUNEL and transmission electron microscopy were employed to estimate the influence of IH764-3 on proliferation and apoptosis of HSCs. The expression of extracellular signal-regulated kinase 1 (ERK1) mRNA and protein in HSCs were detected using RT-PCR and Western blot respectively.
RESULTSIt was showed that H2O2 could promote HSC proliferation. In contrast, IH764-3 at concentrations of 10 mg/L, 20 mg/L, 30 mg/L and 40 mg/L inhibited its proliferation. The inhibition rates were 7.13%, 28.36%, 53.80% and 73.10% (P < 0.01). And the inhibition rates of IH764-3 at concentrations of 30 mg/L at 12 h, 24 h and 48 h were 22.24%, 40.51% and 61.65%. Furthermore, IH764-3 could also induce the HSC apoptosis in dose-dependent an dtime-dependent manners (P < 0.01). In addition, after exposed of HSCs to IH764-3 for 24 h, ERK production decreased and ERK1 mRNA was down-regulated earlier about 2 h after exposure to IH764-3.
CONCLUSIONIH764-3 may inhibit the proliferation and induce apoptosis of HSCs in both dose-dependent and time-dependent manners, which may be related to down-regulation of ERK expression.