Effect of hypoxia inducible factor-1α on thermotolerance against hyperthemia induced cardiomyocytes apoptosis
10.3760/cma.j.issn.0253-3758.2013.09.013
- VernacularTitle:缺氧诱导因子-1α在热耐受对抗高温诱导的大鼠心肌细胞凋亡中的作用
- Author:
Bi-Jun HUANG
1
;
Xiao-Shu CHENG
Author Information
1. 330006,南昌大学第二附属医院心血管内科江西省分子医学重点实验室
- Keywords:
Myocytes,cardiac;
Hypoxia-inducible factor-1,alpha subunit;
Apoptosis;
Thermotolerance
- From:
Chinese Journal of Cardiology
2013;41(9):785-789
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression changes and effects of hypoxia inducible factor1α (HIF-1α) on non-lethal high temperature induced thermotolerance and its role on thermotolerance protection.Methods H9c2 cardiomyocytes were cultured and pretreated with the HIF-1α inhibitor YC-1,the cells were then subjected to normal temperature (37 ℃),thermotolerance induction (40 ℃,3 h),or hyperthermia (43 ℃,2 h).The cells were divided into 8 groups (n =3 each):normal temperature control group ; thermotolerance group ; thermotolerance/hyperthermia group ; hyperthermia group ; DMSO + normal temperature group; YC-1 + thermotolerance group; YC-1 + thermotolerance/hyperthermia group; YC-1 +hyperthermia group.Cell apoptotic rate was assessed by flow cytometry.Western blot was used to detect the expression of HIF-1 α and caspase-3.Results Flow cytometry results showed that apoptosis rate was similar between control group and thermotolerance group,between DMSO + normal temperature group and YC-1 + thermotolerance group,between YC-1 + thermotolerance/hyperthermia group and YC-1 + hyperthermia group,but was significantly higher in hyperthermia group [(17.35 ± 1.07)％] than in control group [(7.52 ± 1.55)％,P ＜ 0.01] which was partly reduced in thermotolerance/hyperthermia group [(12.58 ± 1.97)％,P ＜ 0.01 vs.thermotolerance group].Cell apoptosis rate of YC-1 + thermotolerance/hyperthermia group (23.75 ± 1.92) ％ was significantly higher than that of thermotolerance/hyperthermia group [(12.58 ± 1.97) ％,P ＜ 0.01],and in YC-1 + hyperthermia group [(24.89 ± 1.83) ％] than in hyperthermia group [(17.35 ± 1.07) ％,P ＜ 0.01].HIF-1α expression was obviously upregulated in thermotolerance cells compared with control cells,in thermotolerance/hyperthermia cells than in hyperthermia cells,in YC-1 + thermotolerance group,YC-1 + thermotolerance/hyperthermia group and YC-1 + hyperthermia group than in DMSO group (all P ＜ 0.05).Caspase-3 expression was similar between control group and thermotolerance group,but was significantly lower in thermotolerance/hyperthermia group than in hyperthermia group (P ＜ 0.05),significantly higher in YC-1 + thermotolerance group,YC-1 + thermotolerance/hyperthermia group and YC-1 + hyperthermia group than in DMSO group (all P ＜ 0.05) and significantly higher in YC-1 + thermotolerance/hyperthermia group than in thermotolerance/hyperthermia group (P ＜ 0.01) and in YC-1 + hyperthermia group than in hyperthermia group (P ＜ 0.01).Conclusion Non-lethal high temperature induced thermotolerance can reduce heat stress-induced cardiomyocytes apoptosis rate via upregulating the expression of HIF-1 α and inhibiting caspase-3 signalling pathways.
