Effect of liver X receptor agonist T0901317 on endothelin-1 induced murine HL-1 cardiomyocytes hypertrophy
10.3760/cma.j.issn.0253-3758.2012.02.017
- VernacularTitle:肝X受体信号通路在小鼠HL-1心肌细胞肥大中的作用
- Author:
Jiang LI
1
;
Chun DENG
;
Wen-Juan GU
;
Sai NIE
;
Dao-Quan PENG
;
Shui-Ping ZHAO
Author Information
1. 中南大学湘雅二医院
- Keywords:
Cardiomyopathies;
Endothelin-1;
Liver X receptors
- From:
Chinese Journal of Cardiology
2012;40(2):161-165
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of liver X receptors (LXRs) on endothelin-1 ( ET-1 )induced murine HL-1 cardiomyocytes hypertrophy.Methods Cutured murine HL-1 cardiomyocytes were divided into four experiment groups:①Control group:treated with DMSO ; ②T0901317 group:treated with LXRs agonist T0901317( 1 μmol/L) ; ③ET-1 group:treated with ET-1 ( 1 nmoL/L) ; ④T0901317 + ET-1 group:treated with T0901317 ( 1 μmol/L) for 8 hours,then treated with ET-1 ( 1 nmol/L).Twenty-four hours later,immunofluorescent staining was performed on HL-1 cells,the surface area of HL-1 cells was analyzed with NIH Image J software,and the synthetic rate of protein in HL-1 cells was detected by 3 H-leucine incorporation.The mRNA level of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MyHC ) was measured by quantitative realtime PCR.The effect of T0901317 on mRNA expression of ANP was also detected after LXRs gene silencing.Results The surface area of HL-1 cells,mRNA expression of ANP and β-MyHC,and 3H-leucine incorporation in ET-1 group were 2.00 ± 0.29,1.98 ± 0.47,2.13 ±0.39 and 1.79 ±0.17,respectively,which were singnficantly higher than those of control group ( 1.00 ±0.26,1.00 ±0.21,1.00 ±0.31 and 1.00 ±0.03,respectively,all P ＜0.05).Compared with ET-1 group,the surface area of HL-1 cells,mRNA expression of ANP and β-MyHC,and 3H-leucine incorporation were significantly decreased in T0901317 + ET-1 group ( 1.24 ± 0.25,1.19 ± 0.21,1.48 ± 0.27 and 1.15 ±0.11,respectively,all P ＜ 0.05 ).After inhibition of LXRo/β expression in HL-1 cardiomyocytes using the specific siRNAs,the mRNA expression of ANP in T0901317 + ET-1 group was 1.78 ± 0.05,which was similar as that in ET-1 group ( 1.94 ± 0.17,P ＞ 0.05).Conclusion T0901317,an agonist of LXRs,could inhibit ET-1 induced cardiac hypertrophy in vitro,and LXR Iigand-mediated inhibition on ANP mRNA expression by T0901317 is receptor dependent.
