Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress
Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress
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DOI：
10.1210/en.2006-0073
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发表时间：
2007-02-01
期刊：
影响因子：
4.8
通讯作者：
Feldman, Eva L.
中科院分区：
文献类型：
--
作者：
Vincent, Andrea M.;Perrone, Lorena;Feldman, Eva L.
晚期糖基化终末产物受体（receptor for advanced glycation end products，RECEPTOR）可能通过激活促进氧化应激的细胞内信号通路而促进糖尿病血管和肾脏疾病。氧化应激是高血糖诱导的细胞损伤的介质，是糖尿病并发症的所有机制的统一主题，但很少有关于氧化应激在糖尿病神经病变中的表达和潜在作用的研究。目前的研究表明，背根神经节神经元表达功能性kD，并对kD配体S100产生类似的下游信号传导、氧化应激和细胞损伤，因为其他糖尿病并发症倾向性活动与活性氧簇的形成、半胱天冬酶-3活化和核DNA降解相关。这些事件可以通过抗氧化剂α-硫辛酸治疗来预防。我们的数据表明，旨在减少糖尿病配体，阻断糖尿病信号传导或预防氧化应激的治疗可以显着减少糖尿病患者神经病变的发展。
The receptor for advanced glycation end products ( RAGE) may promote diabetic vascular and renal disease through the activation of intracellular signaling pathways that promote oxidative stress. Oxidative stress is a mediator of hypergly-cemia-induced cell injury and a unifying theme for all mechanisms of diabetic complications, but there are few studies on the expression and potential contribution of RAGE in diabetic neuropathy. The current study demonstrates that dorsal root ganglia neurons express functional RAGE and respond to the RAGE ligand S100 with similar downstream signaling, oxidative stress, and cellular injury as other diabetic complication-prone activity is associated with formation of reactive oxygen species, caspase-3 activation, and nuclear DNA degradation. These events are prevented by treatment with the antioxidant alpha-lipoic acid. Our data indicate that therapies aimed at decreasing RAGE ligands, blocking RAGE signaling, or preventing oxidative stress could significantly decrease the development of neuropathy in diabetic patients.