Bröer S, Rahman B, Pellegri G, Pellerin L, Martin J L, Verleysdonk S, Hamprecht B, Magistretti P J
Physiologisch-chemisches Institut der Universität, Hoppe-Seyler Str. 4, D-72076 Tübingen, Germany.
J Biol Chem. 1997 Nov 28;272(48):30096-102. doi: 10.1074/jbc.272.48.30096.
The transport of lactate is an essential part of the concept of metabolic coupling between neurons and glia. Lactate transport in primary cultures of astroglial cells was shown to be mediated by a single saturable transport system with a Km value for lactate of 7.7 mM and a Vmax value of 250 nmol/(min x mg of protein). Transport was inhibited by a variety of monocarboxylates and by compounds known to inhibit monocarboxylate transport in other cell types, such as alpha-cyano-4-hydroxycinnamate and p-chloromercurbenzenesulfonate. Using reverse transcriptase-polymerase chain reaction and Northern blotting, the presence of mRNA coding for the monocarboxylate transporter 1 (MCT1) was demonstrated in primary cultures of astroglial cells. In contrast, neuron-rich primary cultures were found to contain the mRNA coding for the monocarboxylate transporter 2 (MCT2). MCT1 was cloned and expressed in Xenopus laevis oocytes. Comparison of lactate transport in MCT1 expressing oocytes with lactate transport in glial cells revealed that MCT1 can account for all characteristics of lactate transport in glial cells. These data provide further molecular support for the existence of a lactate shuttle between astrocytes and neurons.
乳酸的转运是神经元与神经胶质细胞之间代谢偶联概念的重要组成部分。星形胶质细胞原代培养物中的乳酸转运由单一的可饱和转运系统介导,该系统对乳酸的Km值为7.7 mM,Vmax值为250 nmol/(分钟×毫克蛋白质)。多种单羧酸盐以及已知可抑制其他细胞类型中单羧酸盐转运的化合物,如α-氰基-4-羟基肉桂酸酯和对氯汞苯磺酸盐,均可抑制转运。通过逆转录聚合酶链反应和Northern印迹法,在星形胶质细胞原代培养物中证实了编码单羧酸盐转运体1(MCT1)的mRNA的存在。相比之下,富含神经元的原代培养物中发现含有编码单羧酸盐转运体2(MCT2)的mRNA。MCT1被克隆并在非洲爪蟾卵母细胞中表达。将表达MCT1的卵母细胞中的乳酸转运与胶质细胞中的乳酸转运进行比较,发现MCT1可以解释胶质细胞中乳酸转运的所有特征。这些数据为星形胶质细胞与神经元之间存在乳酸穿梭提供了进一步的分子支持。