Liu Wenjie, Guo Qulian, Hu Xiaoling, Peng Liangyu, Zhou Bin
Department of Anesthesiology, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008, Changsha, Hunan, China.
Metab Brain Dis. 2015 Jun;30(3):703-9. doi: 10.1007/s11011-014-9622-4. Epub 2014 Oct 16.
Oxidative stress, mitochondrial dysfunction and neuronal apoptosis are thought to be major contributors of Isoflurane toxicity. However, the underlying mechanisms remain largely to be determined. DJ-1, a protein that is involved in the response to various kinds of stress, has shown its neuroprotective effects. Whether DJ-1 has a neuroprotective effect against isoflurane-induced neurotoxocity is still unknown. In this study, we found that expression of DJ-1 is elevated in response to isoflurane treatment in human SH-SY5Y neuroblastoma cells. In order to clarify whether DJ-1 plays a potential role in isoflurane neurotoxicity or as a compensatory response for survival, we investigated the effects of DJ-1 silencing in isoflurane neurotoxicity. Our findings indicate that knockdown of DJ-1 promotes isoflurane-induced oxidative stress and mitochondrial dysfunction. Importantly, DJ-1 silencing was found to exacerbate isoflurane- induced apoptosis through modulation of mitochondria-dependent apoptosis pathways, thereby suggesting that induction of DJ-1 in response to isoflurane might act as a compensatory response for cell survival.
氧化应激、线粒体功能障碍和神经元凋亡被认为是异氟烷毒性的主要促成因素。然而，其潜在机制在很大程度上仍有待确定。DJ-1是一种参与应对各种应激反应的蛋白质，已显示出其神经保护作用。DJ-1是否对异氟烷诱导的神经毒性具有神经保护作用仍不清楚。在本研究中，我们发现人SH-SY5Y神经母细胞瘤细胞经异氟烷处理后DJ-1的表达升高。为了阐明DJ-1在异氟烷神经毒性中是否发挥潜在作用或作为一种生存的代偿反应，我们研究了DJ-1沉默对异氟烷神经毒性的影响。我们的研究结果表明，敲低DJ-1会促进异氟烷诱导的氧化应激和线粒体功能障碍。重要的是，发现DJ-1沉默会通过调节线粒体依赖性凋亡途径加剧异氟烷诱导的凋亡，从而表明异氟烷诱导的DJ-1可能作为细胞生存的代偿反应。
