College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, 210095, China.
Mol Cell Biochem. 2017 Nov;435(1-2):73-86. doi: 10.1007/s11010-017-3058-1. Epub 2017 May 11.
We investigated the effects of co-enzyme Q10 (Q10) and acetyl salicylic acid (ASA) on expression of Hsp70 in the protection of primary chicken myocardial cells during heat stress. Western blot analysis showed that Q10 and ASA accelerated the induction of Hsp70 when chicken myocardial cells were exposed to hyperthermia. In the absence of heat stress, however, neither Q10 nor ASA are able to upregulate Hsp70 expression. Analysis of enzymes that respond to cellular damage and pathological examination revealed that ectopic expression of ASA and Q10 alleviate cellular damage during heat stress. Quantification of heat shock factors (HSF) indicated that treatment of ASA increased the expression of HSF-1 and HSF-3 during heat stress. Treatment with Q10 resulted in the elevation of HSF-1 expression. Expression of HSF-2 and HSF-4 was not affected by ASA or Q10. Subcellular distribution analysis of HSF-1 and HSF-3 showed that in response to heat stress ASA promoted nuclear translocation of HSF-1 and HSF-3, while Q10 promoted only HSF-1 nuclear translocation. Chromatin immunoprecipitation (ChIP) analysis indicated that HSF-1 occupies the Hsp70 promoter in chicken primary myocardial cells during heat stress and under normal conditions, while HSF-3 occupies the Hsp70 promoter only during heat stress. Real-time PCR analysis revealed that ASA induces HSF-1 and HSF-3 binding to Hsp70 HSE, while Q10 only induces HSF1 binding to Hsp70 HSE, in agreement with the impact of HSF1 and HSF3 silencing on Hsp70 expression. These data demonstrate that ASA and Q10 both induce the expression of Hsp70 to protect chicken primary myocardial cells during heat stress, but through distinct pathways.
我们研究了辅酶 Q10(Q10)和乙酰水杨酸(ASA)对热应激时原代鸡心肌细胞中 HSP70 表达的影响。Western blot 分析显示,当鸡心肌细胞暴露于高温时,Q10 和 ASA 加速了 HSP70 的诱导。然而,在没有热应激的情况下,Q10 和 ASA 都不能上调 HSP70 的表达。对细胞损伤和病理检查的酶分析表明,ASA 和 Q10 的异位表达减轻了热应激时的细胞损伤。热休克因子(HSF)的定量分析表明,ASA 处理增加了热应激时 HSF-1 和 HSF-3 的表达。Q10 处理导致 HSF-1 表达升高。ASA 或 Q10 对 HSF-2 和 HSF-4 的表达没有影响。HSF-1 和 HSF-3 的亚细胞分布分析表明,热应激时 ASA 促进了 HSF-1 和 HSF-3 的核转位,而 Q10 仅促进了 HSF-1 的核转位。染色质免疫沉淀(ChIP)分析表明,HSF-1 在热应激和正常条件下占据鸡原代心肌细胞中 HSP70 启动子,而 HSF-3 仅在热应激时占据 HSP70 启动子。实时 PCR 分析显示,ASA 诱导 HSF-1 和 HSF-3 与 Hsp70 HSE 结合,而 Q10 仅诱导 HSF1 与 Hsp70 HSE 结合,与 HSF1 和 HSF3 沉默对 Hsp70 表达的影响一致。这些数据表明,ASA 和 Q10 都能诱导 HSP70 的表达,以保护鸡原代心肌细胞在热应激时,但通过不同的途径。