高血糖通过过度激活 Toll 样受体 4 加剧氧化低密度脂蛋白诱导的许旺细胞死亡

IF 3.2 Q2 CLINICAL NEUROLOGY
Wataru Nihei, Ayako Kato, Tatsuhito Himeno, Masaki Kondo, Jiro Nakamura, Hideki Kamiya, Kazunori Sango, Koichi Kato
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引用次数: 0

摘要

低密度脂蛋白水平升高是糖尿病神经病变的危险因素。糖尿病与代谢应激升高有关,导致氧化低密度脂蛋白的形成。因此,研究糖尿病并发血脂异常和氧化低密度脂蛋白水平升高时糖尿病神经病变的发病机制非常重要。在此,我们研究了高血糖和氧化低密度脂蛋白处理对许旺细胞死亡的影响及其内在机制。在正常或高血糖条件下,用氧化低密度脂蛋白处理永生小鼠许旺细胞。我们观察到,与正常血糖条件相比,高血糖条件下氧化低密度脂蛋白诱导的细胞死亡增加。此外,高血糖和氧化低密度脂蛋白会协同上调toll样受体4的基因和蛋白表达。使用选择性收费样受体4信号抑制剂TAK-242进行预处理可减轻高血糖和氧化低密度脂蛋白诱导的细胞死亡和细胞凋亡Caspase-3通路。我们的研究结果表明,高血糖和氧化低密度脂蛋白水平升高导致的toll样受体4信号的过度激活会协同加剧糖尿病神经病变;因此,它可以成为糖尿病神经病变的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hyperglycaemia Aggravates Oxidised Low-Density Lipoprotein-Induced Schwann Cell Death via Hyperactivation of Toll-like Receptor 4.

Increased low-density lipoprotein levels are risk factors for diabetic neuropathy. Diabetes mellitus is associated with elevated metabolic stress, leading to oxidised low-density lipoprotein formation. Therefore, it is important to investigate the mechanisms underlying the pathogenesis of diabetic neuropathy in diabetes complicated by dyslipidaemia with increased levels of oxidised low-density lipoprotein. Here, we examined the effects of hyperglycaemia and oxidised low-density lipoprotein treatment on Schwann cell death and its underlying mechanisms. Immortalised mouse Schwann cells were treated with oxidised low-density lipoprotein under normo- or hyperglycaemic conditions. We observed that oxidised low-density lipoprotein-induced cell death increased under hyperglycaemic conditions compared with normoglycaemic conditions. Moreover, hyperglycaemia and oxidised low-density lipoprotein treatment synergistically upregulated the gene and protein expression of toll-like receptor 4. Pre-treatment with TAK-242, a selective toll-like receptor 4 signalling inhibitor, attenuated hyperglycaemia- and oxidised low-density lipoprotein-induced cell death and apoptotic caspase-3 pathway. Our findings suggest that the hyperactivation of toll-like receptor 4 signalling by hyperglycaemia and elevated oxidised low-density lipoprotein levels synergistically exacerbated diabetic neuropathy; thus, it can be a potential therapeutic target for diabetic neuropathy.

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来源期刊
Neurology International
Neurology International CLINICAL NEUROLOGY-
CiteScore
3.70
自引率
3.30%
发文量
69
审稿时长
11 weeks
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