Transport mechanism for L-lactic acid in human myocytes using human prototypic embryonal rhabdomyosarcoma cell line (RD cells)
Transport mechanism for L-lactic acid in human myocytes using human prototypic embryonal rhabdomyosarcoma cell line (RD cells)
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DOI：
10.1248/bpb.28.1197
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发表时间：
2005-07-01
影响因子：
2
通讯作者：
Iseki, K
中科院分区：
文献类型：
--
作者：
Kobayashi, M;Fujita, I;Iseki, K
单羧酸转运蛋白（MCT）是一种跨膜转运乳酸和质子的蛋白质，对调节肌肉pH值有重要作用，但MCT亚型是否参与了乳酸在骨骼肌中的转运尚不清楚。本研究的目的是使用人横纹肌肉瘤（RD）细胞系作为人骨骼肌模型来表征L-乳酸转运。发现MCT 1、2和4的mRNA在RD细胞中表达。[C-14] L-乳酸摄取呈浓度依赖性，K-m为1.19 mm。该K-m值与MCTI或MCT 2的K-m值相当。MCT 1 mRNA的表达量明显高于MCT 2。因此，MCTI最可能作用于RD细胞的L-乳酸摄取。[C-14] α-氰基-4-羟基肉桂酸酯（CHC）可抑制RD细胞中的L-乳酸外排，但MCT 1的底物丁酸不抑制。因此，MCT 2或MCT 4负责RD细胞的L-乳酸流出。发现MCT 4 mRNA的存在显著大于MCT 2。我们的结论是，MCTI是负责L-乳酸的摄取和L-乳酸的流出是由MCT 4介导的RD细胞。
Monocarboxylate transporter (MCT), which cotransport L-lactic acid and protons across cell membranes, are important for regulation of muscle pH. However, it has not been demonstrated in detail whether MCT isoform contribute to the transport Of L-lactic acid in skeletal muscle. The aim of this study was to characterize L-lactic acid transport using an human rhabdomyosarcoma (RD) cell line as a model of human skeletal muscle. mRNAs of MCT 1, 2 and 4 were found to be expressed in RD cells. The [C-14] L-lactic acid uptake was concentration-dependent with a K-m of 1.19 mm. This K-m value was comparable to its K-m values for MCTI or MCT2. MCT1 mRNA was found to be present markedly greater than that MCT2. Therefore, MCTI most probably acts on L-lactic acid uptake at RD cells. [C-14] L-Lactic acid efflux in RD cells was inhibited by alpha-cyano-4-hydroxycinnamate (CHC) but not by butyric acid, a substrate of MCT1. Accordingly, MCT2 or MCT4 is responsible for L-lactic acid efflux by RD cells. MCT4 mRNA was found to be present significantly greater than that MCT2. We conclude that MCTI is responsible for L-lactic acid uptake and L-lactic acid efflux is mediated by MCT4 in RD cells.