Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes
Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes
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DOI：
10.1042/0264-6021:3410529
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发表时间：
1999-08-01
影响因子：
4.1
通讯作者：
Deitmer, JW
中科院分区：
文献类型：
--
作者：
Bröer, S;Bröer, A;Deitmer, JW
在脑细胞和心肌细胞中对乳酸转运的观察表明存在高亲和力的单羧酸转运体。通过在非洲爪蟾卵母细胞中的表达分析了大鼠单羧酸转运蛋白亚型MCT 2，并将结果与已知的心脏和大脑中乳酸转运的特征进行了比较。通过MCT 2的单羧酸转运由质膜上的H+梯度驱动。乳酸的摄取强烈增加，pH值降低，显示在pH 7.2的半最大刺激。各种各样的单羧酸盐和酮体，包括乳酸盐、丙酮酸盐、β-羟基丁酸盐、乙酰乙酸盐、2-氧代异戊酸盐和2-氧代异己酸盐，都是MCT 2的底物。所有底物对MCT 2均具有高亲和力。对于乳酸盐，在pH 7.0下测定的Km值为0.74 +/- 0.07 mM。对于其他底物，测定了100 μ M和1 mM之间的K-i值对乳酸转运的抑制作用，其约为普遍表达的单羧酸转运蛋白亚型MCT 1的相应值的十分之一。α-氰基-4-羟基肉桂酸、阴离子通道抑制剂和黄酮类化合物可抑制通过MCT 2的单羧酸转运。提示表达MCT 2的细胞优先使用乳酸和酮体作为能量来源。
Observations on lactate transport in brain cells and cardiac myocytes indicate the presence of a high-affinity monocarboxylate transporter. The rat monocarboxylate transporter isoform MCT2 was analysed by expression in Xenopus laevis oocytes and the results were compared with the known characteristics of lactate transport in heart and brain. Monocarboxylate transport via MCT2 was driven by the H+ gradient over the plasma membrane. Uptake of lactate strongly increased with decreasing pH, showing half-maximal stimulation at pH 7.2. A wide variety of monocarboxylates and ketone bodies, including lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, 2-oxoiso-valerate and 2-oxoisohexanoate, were substrates of MCT2. All substrates had a high affinity for MCT2, For lactate a K-m value of 0.74 +/- 0.07 mM was determined at pH 7.0. For the other substrates, K-i values between 100 mu M and 1 mM were measured for inhibition of lactate transport, which is about one-tenth of the corresponding values for the ubiquitously expressed monocarboxylate transporter isoform MCT1. Monocarboxylate transport via MCT2 could be inhibited by alpha-cyano-4-hydroxycinnamate, anion-channel inhibitors and flavonoids. It is suggested that cells which express MCT2 preferentially use lactate and ketone bodies as energy sources.