Huang Shang-Ming, Hsu Chin-Lin, Chuang Hong-Chih, Shih Ping-Hsiao, Wu Chi-Hao, Yen Gow-Chin
Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
Neurotoxicology. 2008 Nov;29(6):1016-22. doi: 10.1016/j.neuro.2008.07.002. Epub 2008 Jul 25.
Methylglyoxal is a reactive dicarbonyl compound generated as an intermediate of glycolysis during the physical glycation in the diabetic condition. It is considered to be a potent precursor of advanced glycation end products (AGEs) formation. Methylglyoxal itself and methylglyoxal-derived AGEs have been commonly implicated in the development of diabetic neuropathy. Our previous study indicated that vanillic acid showed an inhibitory effect against methylglyoxal-mediated Neuro-2A cell apoptosis, suggesting that vanillic acid might possess cytoprotective properties in the prevention of diabetic neuropathy complication. In this study, the effects of vanillic acid on the methylglyoxal-mediated glycation system involved in the progression of Neuro-2A cell apoptosis were further investigated. Our findings indicated that methylglyoxal-induced Neuro-2A cell apoptosis was mediated through the possible glycation mechanism of oxidative stress, activation of the MAPK signaling pathway (p38 and JNK) and oxidation-sensitive protein expression (PKC and p47(phox)) and methylglyoxal-derived N-epsilon-(carboxymethyl)lysine (CML) formation. Vanillic acid, however, suppressed methylglyoxal-induced Neuro-2A cell apoptosis via inhibition of glycation mechanisms including ROS, p38 and JNK, PKC and p47(phox), and methylglyoxal-derived CML formation. In the present study, we established the first evidence that vanillic acid might contribute to the prevention of the development of diabetic neuropathy by blocking the methylglyoxal-mediated intracellular glycation system.
甲基乙二醛是一种反应性二羰基化合物，在糖尿病状态下的物理糖基化过程中作为糖酵解的中间产物生成。它被认为是晚期糖基化终产物（AGEs）形成的有力前体。甲基乙二醛本身以及甲基乙二醛衍生的AGEs通常与糖尿病神经病变的发展有关。我们之前的研究表明，香草酸对甲基乙二醛介导的Neuro-2A细胞凋亡具有抑制作用，这表明香草酸在预防糖尿病神经病变并发症方面可能具有细胞保护特性。在本研究中，进一步研究了香草酸对参与Neuro-2A细胞凋亡进程的甲基乙二醛介导的糖基化系统的影响。我们的研究结果表明，甲基乙二醛诱导的Neuro-2A细胞凋亡是通过氧化应激的可能糖基化机制、MAPK信号通路（p38和JNK）的激活以及氧化敏感蛋白表达（PKC和p47(phox)）和甲基乙二醛衍生的N-ε-(羧甲基)赖氨酸（CML）形成介导的。然而，香草酸通过抑制包括ROS、p38和JNK、PKC和p47(phox)以及甲基乙二醛衍生的CML形成等糖基化机制，抑制了甲基乙二醛诱导的Neuro-2A细胞凋亡。在本研究中，我们首次证实香草酸可能通过阻断甲基乙二醛介导的细胞内糖基化系统，有助于预防糖尿病神经病变的发展。
