Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore.
Biochem Biophys Res Commun. 2019 May 21;513(1):22-27. doi: 10.1016/j.bbrc.2019.02.122. Epub 2019 Mar 28.
Ergothioneine is a biologically important compound that has been shown to be transported by the organic cation transporter novel type 1 (OCTN1). Following this discovery, a variety of alternate functions for OCTN1 have been suggested including an integral function in the extra-neuronal cholinergic system. The present study reaffirms the primacy of ergothioneine over these alternate substrates using natively expressed OCTN1 in HeLa cells. Besides the general transport inhibitors, quinidine, verapamil and pyrilamine no other putative substrate inhibited ergothioneine transport significantly, with only a slight inhibition demonstrated by carnitine. Even compounds structurally similar to ergothioneine failed to inhibit ergothioneine uptake, suggesting high selectivity of OCTN1. Ergothioneine was found to be avidly accumulated even at low concentrations (300 nM) by HeLa cells.
ergothioneine 是一种具有重要生物学意义的化合物，已被证明可通过新型有机阳离子转运蛋白 1（OCTN1）进行转运。在此发现之后，OCTN1 的各种替代功能被提出，包括在非神经元胆碱能系统中的重要功能。本研究使用 HeLa 细胞中天然表达的 OCTN1，再次证实了 ergothioneine 对这些替代底物的优先性。除了一般的转运抑制剂奎尼丁、维拉帕米和哌嗪外，没有其他假定的底物能显著抑制 ergothioneine 的转运，只有肉碱表现出轻微的抑制作用。即使是结构上与 ergothioneine 相似的化合物也不能抑制 ergothioneine 的摄取，这表明 OCTN1 的选择性很高。ergothioneine 甚至在低浓度（300 nM）时也能被 HeLa 细胞强烈积累。
