Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-10 and nerve growth factor in cultured hippocampal neuronal cells
Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-10 and nerve growth factor in cultured hippocampal neuronal cells
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DOI：
10.1016/j.brainres.2004.01.066
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发表时间：
2004-05-01
期刊：
影响因子：
2.9
通讯作者：
Amicarelli, F
中科院分区：
文献类型：
--
作者：
Di Loreto, S;Caracciolo, V;Amicarelli, F
甲基乙二醛(MG)是蛋白质和其他重要细胞成分最强大的糖基化试剂之一，已被证明对培养细胞有毒性。在高血糖条件下，已经观察到人体体液和组织中MG浓度的增加，这似乎是糖尿病并发症的原因。最近的数据表明，根据一种涉及氧化应激和晚期糖基化终产物(AGE)形成的机制，糖尿病可能会导致认知过程的损害。在本研究中，我们通过研究MG对急性时相反应的主要诱导物白介素1β(IL-1β)和神经生长因子(NGF)表达的影响，探讨了MG对神经细胞毒性的分子机制。实验是在培养的大鼠海马神经细胞上进行的，海马区是一个主要参与认知过程的脑区，因此可能是糖尿病导致认知能力受损的靶点。结果表明，MG治疗引起海马神经细胞广泛、氧化应激介导的细胞死亡，导致过氧化氢酶强烈的酶活性和蛋白抑制作用。MG还导致NGF的转录和蛋白表达以及促炎细胞因子IL-1β的表达显著增加。镁与抗氧化剂N-乙酰半胱氨酸(NAC)的共同处理完全取消了所观察到的作用。综上所述，这些数据表明海马神经元对MG介导的氧化应激非常敏感。(C)2004爱思唯尔B.V.保留所有权利。
Methylglyoxal (MG) is one of the most powerful glycating agents of proteins and other important cellular components and has been shown to be toxic to Cultured cells. Under hyperglycaemic conditions, an increase in the concentration of MG has been observed in human body fluids and tissues that seems to be responsible for diabetic complications. Recent data suggest that diabetes may cause impairment of cognitive processes, according to a mechanism involving both oxidative stress and advanced glycation end product (AGE) formation. In this work, we explored the molecular mechanism underlying MG toxicity in neural cells, by investigating the effect of MG on both the interleukin-1beta (IL-1beta), as the major inducer of the acute phase response, and the nervous growth factor (NGF) expression. Experiments were performed on Cultured neural cells from rat hippocampus, being this brain region mostly involved in cognitive processes and, therefore, possible target of diabetes-mediated impairment of cognitive abilities. Results show that MG treatment causes in hippocampal neural cells extensive, oxidative stress-mediated cell death, in consequence of a strong catalase enzymatic activity and protein inhibition. MG also causes a very significant increase in both transcript and protein expression of the NGF as well as of the pro-inflammatory cytokine IL-1beta. MG co-treatment with the antioxidant N-acetylcysteine (NAC) completely abrogates the observed effects. Taken together, these data demonstrate that hippocampal neurons are strongly Susceptible to MG-mediated oxidative stress. (C) 2004 Elsevier B.V. All rights reserved.