Yao Xiangyang, Bai Qin, Yan Dazhong, Li Guilan, Lü Chaotian, Xu Hui
Department of Biology and Food Engineering, Bengbu College, Bengbu, PR China.
Department of Biology and Food Engineering, Bengbu College, Bengbu, PR China.
Toxicol In Vitro. 2015 Apr;29(3):600-8. doi: 10.1016/j.tiv.2015.01.009. Epub 2015 Jan 31.
In present study, we showed that the mRNA and protein levels of HO-1 and Hsp70 in solanesol-treated L02 cells were significantly increased. The induction of the HO-1 by solanesol is majorly achieved via enhancing the nuclear translocation and transactivity of Nrf2 through enhancement of Hsp90-Keap1 interaction, while solanesol-elevated Hsp70 is related with promoting the nuclear translocation of HSF1 through the involvement of chaperones interaction. Furthermore, the induction of HO-1 and Hsp70 by solanesol could protect against ethanol-induced liver injury, including significantly suppressing the elevation of the activities of LDH and AST, attenuating ethanol-induced increase of the MDA, ROS level and decrease of the GSH level. Moreover, solanesol also suppressed ethanol-induced apoptosis of L02 cells by inhibition of nuclear morphological damage, procaspase 3 and cleavage of caspase 3 and PARP, suggesting solanesol may be beneficial against ALD. Solanesol also promoted tBHQ-mediated protective effects. However, treatment cells with SnPP or PES markedly abrogated the protective effects of solanesol on ethanol-induced cell injury. These results strongly suggested that solanesol could protect ethanol-induced L02 cell damage, which might be attributed to the activation of HO-1 and Hsp70.
在本研究中，我们发现经茄尼醇处理的L02细胞中HO-1和Hsp70的mRNA及蛋白水平显著升高。茄尼醇对HO-1的诱导主要是通过增强Hsp90与Keap1的相互作用，从而增强Nrf2的核转位及转录活性来实现的，而茄尼醇升高Hsp70则与通过伴侣蛋白相互作用促进HSF1的核转位有关。此外，茄尼醇对HO-1和Hsp70的诱导可预防乙醇诱导的肝损伤，包括显著抑制LDH和AST活性的升高，减轻乙醇诱导的MDA、ROS水平升高以及GSH水平降低。此外，茄尼醇还通过抑制核形态损伤、procaspase 3以及caspase 3和PARP的裂解来抑制乙醇诱导的L02细胞凋亡，提示茄尼醇可能对酒精性肝病有益。茄尼醇还增强了叔丁基对苯二酚介导的保护作用。然而，用SnPP或PES处理细胞显著消除了茄尼醇对乙醇诱导的细胞损伤的保护作用。这些结果强烈表明，茄尼醇可保护乙醇诱导的L02细胞损伤，这可能归因于HO-1和Hsp70的激活。
