Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing 400016, China.
Faculty of Medical Technology, Chongqing Medical and Pharmaceutical College , Chongqing 401331, China.
J Proteome Res. 2018 Jan 5;17(1):305-314. doi: 10.1021/acs.jproteome.7b00579. Epub 2017 Nov 8.
Epilepsy is a difficult-to-manage neurological disease that can result in organ damage, such as cardiac injury, that contributes to sudden unexpected death in epilepsy (SUDEP). Although recurrent seizure-induced cardiac dysregulation has been reported, the underlying molecular mechanisms are unclear. We established an epileptic model with Sprague-Dawley rats by applying isobaric tags for a relative and absolute quantification (iTRAQ)-based proteomics approach to identify differentially expressed proteins in myocardial tissue. A total of seven proteins in the acute epilepsy group and 60 proteins in the chronic epilepsy group were identified as differentially expressed. Bioinformatics analysis suggested that the pathogenesis of cardiac injury in acute and chronic epilepsy may be due to different molecular mechanisms. Three proteins, a receptor for activated protein kinase C1 (RACK1), aldehyde dehydrogenase 6 family member A1 (ALDH6A1), and glycerol uptake/transporter 1 (Hhatl), were identified as playing crucial roles in cardiac injury during epilepsy and were successfully confirmed by Western blot and immunohistochemistry analysis. Our study not only provides a deeper understanding of the pathophysiological mechanisms of myocardial damage in epilepsy, but also suggests some potential novel therapeutic targets for preventing cardiac injury and reducing the incidence of sudden death due to heart failure.
癫痫是一种难以控制的神经系统疾病，可导致心脏损伤等器官损伤，从而导致癫痫猝死 (SUDEP)。虽然已经报道了反复癫痫发作引起的心脏失调，但潜在的分子机制尚不清楚。我们通过应用等压标签相对和绝对定量 (iTRAQ) 蛋白质组学方法，建立了 Sprague-Dawley 大鼠癫痫模型，以鉴定心肌组织中差异表达的蛋白质。在急性癫痫组中鉴定到 7 种差异表达蛋白，在慢性癫痫组中鉴定到 60 种差异表达蛋白。生物信息学分析表明，急性和慢性癫痫中心脏损伤的发病机制可能是由于不同的分子机制。三种蛋白质，蛋白激酶 C1 激活受体 (RACK1)、醛脱氢酶 6 家族成员 A1 (ALDH6A1) 和甘油摄取/转运蛋白 1 (Hhatl)，被鉴定为在癫痫发作期间对心脏损伤起关键作用，并通过 Western blot 和免疫组织化学分析成功得到证实。我们的研究不仅深入了解了癫痫中心肌损伤的病理生理机制，还为预防心脏损伤和降低心力衰竭导致猝死的发生率提供了一些潜在的新的治疗靶点。
