Myocardial protection of a novel histone deacetylase inhibitor against hypoxia injury
10.7644/j.issn.1674-9960.2015.01.007
- VernacularTitle:新型组蛋白去乙酰化酶抑制剂对缺氧损伤心肌细胞的保护作用研究
- Author:
Yanbing WANG
;
Suping REN
;
Qingjun WANG
;
Zhixin QIAO
;
Chunyan WANG
;
Qiyuan KUAI
;
Yu WANG
;
Xuanlin WANG
;
Min HE
;
Weijing LI
;
Liwei SUN
;
Qun YU
- Publication Type:Journal Article
- Keywords:
histone deacetylase inhibitor;
JZ005;
hypoxia;
myocytes,cardiac;
cytoprotection;
chemiluminescent measurements
- From:
Military Medical Sciences
2015;(1):30-35,70
- CountryChina
- Language:Chinese
-
Abstract:
Objective To verify enzyme activity inhibition of a novel histone deacetylase inhibitor ( HDACi ) JZ005 using an HDACi chemiluminescence detection kit and a cell-based screening model .Methods The plasmid with p21 gene promoter elements and luciferase reporter gene was transfected into human embryonic kidney cells 293 , and the stable transfectants were established by G418 screening.Enzyme activity inhibition of JZ005 on histone deacetylases (HDACs) was verified by the HDACi chemiluminescence detection kit and the cell-based screening model .A well-known HDACi , tri-chostatin A ( TSA) was used as the positive control .MTT assay was used to detect the protection of rat H 9c2 myocardial cells suffering from CoCl 2-induced hypoxia and treated with different concentrations of JZ 005 .The expression of acetylated histone H3 protein of normal and CoCl 2-induced hypoxia H9c2 cells before and after JZ005 treatment was assayed by West-ern blotting while the effect of drug administration on apoptosis was detected by flow cytometry ( FCM) .Results An HDA-Ci cell-based screening system targeting the p21 gene promoter was ranging established .The JZ005, a HDACi, markedly suppressed the activity of HDACs by more than 50%with the concentration ranging from 50 to 400 μmol/L.JZ005 signifi-cantly protected H9c2 cells from hypoxia injury .Cell viability was increased by 38.33%,56.00% and 35.20% compared with control,accompanied by an enhanced acetylation level of histone H 3.JZ005(25,50 and 100 μmol/L) treatment sig-nificantly decreased the number of apoptotic cells (6.63%,10.56% and 8.89%) compared to control group (12.89%). Conclusion An HDACi cell-based screening system is successfully established .JZ005 effectively protects myocardial cells against hypoxia injury while enhancing the acetylation level of histone H 3.Our results indicate that JZ005 might be developed as a potential drug for hypoxia treatment .
