Protection from diabetes-induced peripheral sensory neuropathy--a role for elevated glyoxalase I?
Protection from diabetes-induced peripheral sensory neuropathy--a role for elevated glyoxalase I?
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DOI：
10.1016/j.expneurol.2011.12.015
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发表时间：
2012-03
影响因子：
5.3
通讯作者：
Wright, D. E.
中科院分区：
文献类型：
--
作者：
Jack, M. M.;Ryals, J. M.;Wright, D. E.
关键词：
糖尿病神经病变是糖尿病的常见并发症，超过一半的患者由于感觉神经损伤而出现神经病变症状。糖尿病诱导的高血糖导致晚期糖基化终产物（AGEs）的加速产生，其改变蛋白质，从而导致神经元功能障碍。谷胱甘肽酶系统，特别是谷胱甘肽酶I（GLO 1），负责解毒AGEs的前体，如甲基乙二醛和其他反应性二羰基化合物。本研究的目的是确定GLO 1的表达差异是否可能在糖尿病感觉神经病变的发展中发挥作用。BALB/cJ小鼠天然表达低水平的GLO 1，而BALB/cByJ在相似的遗传背景下由于GLO 1拷贝数的增加而表达约10倍高的水平。STZ注射后5周，糖尿病BALB/cJ小鼠的机械阈值增加了68%，这是无感觉神经病变或机械敏感性丧失的特征。这种行为变化与表皮内神经纤维密度（IENFD）减少38%相关。糖尿病BALB/cJ小鼠也减少了83%和47%，分别在复合物I和V的线粒体氧化磷酸化蛋白的表达。相反，糖尿病BALB/cByJ小鼠没有出现神经病变、IENFD变化或线粒体蛋白表达改变的体征。GLO 1表达减少与糖尿病诱导的高血糖配对可能导致神经元线粒体损伤和糖尿病神经病变的症状。因此，AGEs、谷胱甘肽酶系统和线粒体功能障碍可能在糖尿病周围神经病变的发展和调节中发挥作用。
Diabetic neuropathy is a common complication of diabetes mellitus with over half of all patients developing neuropathy symptoms due to sensory nerve damage. Diabetes-induced hyperglycemia leads to the accelerated production of advanced glycation end products (AGEs) that alter proteins, thereby leading to neuronal dysfunction. The glyoxalase enzyme system, specifically glyoxalase I (GLO1), is responsible for detoxifying precursors of AGEs, such as methylglyoxal and other reactive dicarbonyls. The purpose of our studies was to determine if expression differences of GLO1 may play a role in the development of diabetic sensory neuropathy. BALB/cJ mice naturally express low levels of GLO1, while BALB/cByJ express approximately 10-fold higher levels on a similar genetic background due to increased copy numbers of GLO1. Five weeks following STZ injection, diabetic BALB/cJ mice developed a 68% increase in mechanical thresholds, characteristic of insensate neuropathy or loss of mechanical sensitivity. This behavior change correlated with a 38% reduction in intraepidermal nerve fiber density (IENFD). Diabetic BALB/cJ mice also had reduced expression of mitochondrial oxidative phosphorylation proteins in Complex I and V by 83% and 47%, respectively. Conversely, diabetic BALB/cByJ mice did not develop signs of neuropathy, changes in IENFD, or alterations in mitochondrial protein expression. Reduced expression of GLO1 paired with diabetes-induced hyperglycemia may lead to neuronal mitochondrial damage and symptoms of diabetic neuropathy. Therefore, AGEs, the glyoxalase system, and mitochondrial dysfunction may play a role in the development and modulation of diabetic peripheral neuropathy.
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影响因子：
7.4
作者：
Johnson MS;Ryals JM;Wright DE
通讯作者：
Wright DE
影响因子：
5.3
作者：
SPARKES, RS;SPARKES, MC;ANDERSON, CE
通讯作者：
ANDERSON, CE
影响因子：
8.2
作者：
Brouwers, O.;Niessen, P. M.;Haenen, G.;Miyata, T.;Brownlee, M.;Stehouwer, C. D.;De Mey, J. G.;Schalkwijk, C. G.
通讯作者：
Schalkwijk, C. G.
影响因子：
7.7
作者：
Muller, Karra A.;Ryals, Janelle M.;Wright, Douglas E.
通讯作者：
Wright, Douglas E.
影响因子：
4.2
作者：
de Arriba, Susana Garcia;Stuchbury, Grant;Muench, Gerald
通讯作者：
Muench, Gerald