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首页> 外文期刊>The Journal of toxicological sciences >Methylglyoxal activates the human transient receptor potential ankyrin 1 channel.
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Methylglyoxal activates the human transient receptor potential ankyrin 1 channel.

机译：甲基乙二醛激活人瞬时受体电位锚蛋白1通道。

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摘要

Methylglyoxal (MG) is an endogenous carbonyl compound that is produced in large quantity under hyperglycemic conditions, which are believed to contribute to the development of diabetic neuropathy. However, the mechanism by which this occurs and the molecular targets of MG are unclear. In the present study, we investigated the effect of MG on transient receptor potential ankyrin 1 (TRPA1) activation in human TRPA1-expressing HEK293 cells. MG activated TRPA1-expressing HEK293 cells, but failed to activate human capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1)-expressing HEK293 cells or mock-transfected HEK293 cells. MG also induced calcium (Ca(2+)) influx in a concentration-dependent manner, and the concentration-response curve indicates that the effect of MG has an EC(50) of 343.1 ± 17.3 μM. Interestingly, the time course in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in human TRPA1-expressing HEK293 showed considerable differences in response to MG and cinnamaldehyde. Furthermore, we examined four endogenous carbonyl compounds, including MG, glyceraldehyde, glycolaldehyde, and glyoxal; only MG notably activated TRPA1-expressing HEK293 cells. These results may provide insight into the TRPA1-mediated effects of MG on diabetic neuropathy.
机译：甲基乙二醛（MG）是在高血糖条件下大量产生的内源性羰基化合物，据信这有助于糖尿病性神经病的发展。但是，尚不清楚其发生的机理和MG的分子靶标。在本研究中，我们研究了MG对表达人TRPA1的HEK293细胞中瞬时受体电位锚蛋白1（TRPA1）活化的影响。 MG激活表达TRPA1的HEK293细胞，但未能激活表达人辣椒素敏感的瞬时受体电位类香草素1（TRPV1）的HEK293细胞或模拟转染的HEK293细胞。 MG还以浓度依赖的方式诱导钙（Ca（2+））流入，并且浓度-响应曲线表明MG的作用具有343.1±17.3μM的EC（50）。有趣的是，在人类TRPA1表达HEK293的细胞内Ca（2+）浓度（[Ca（2 +）]（i））中的时间过程显示出对MG和肉桂醛的显着差异。此外，我们研究了四种内源性羰基化合物，包括MG，甘油醛，乙醇醛和乙二醛。仅MG显着激活了表达TRPA1的HEK293细胞。这些结果可能提供洞察MG的TRPA1介导的糖尿病神经病。

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