Mechanism of L-lactic acid transport in L6 skeletal muscle cells.
Mechanism of L-lactic acid transport in L6 skeletal muscle cells.
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DOI：
10.2133/dmpk.19.363
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发表时间：
2004-10-01
影响因子：
2.1
通讯作者：
Iseki, Ken
中科院分区：
文献类型：
--
作者：
Kobayashi, Masaki;Itagaki, Shirou;Iseki, Ken
L-乳酸转运在L-乳酸进出肌肉循环的调节中起着重要作用。为了阐明L-乳酸在骨骼肌中的转运机制，使用L 6细胞系研究L-乳酸摄取。发现L 6细胞表达单羧酸转运体（MCT）1、2和4的mRNA。L 6细胞对[（14）C] L-乳酸的摄取增加至pH 6.0。在pH 6.0时，[（14）C] L-乳酸的摄取呈浓度依赖性，K（m）为3.7 mM。该过程可被α-氰基-4-羟基肉桂酸盐（一种典型的MCT 1、2和4抑制剂）还原。这些结果表明，MCT参与L 6细胞摄取L-乳酸。[（14）C] L-乳酸摄取被单羧酸和单羧酸药物显著抑制，但不被二羧酸和氨基酸抑制。此外，苯甲酸，一种底物的MCT 1，竞争性抑制这一进程的K（i）为1.7 mM。[（14）C] L-乳酸流出在L 6细胞被抑制α-氰基-4-羟基肉桂酸，但不被苯甲酸。这些结果表明，L 6细胞中的[（14）C] L-乳酸外排由MCT而非MCT 1介导。
L-lactic acid transport plays an important role in the regulation of L-lactic acid circulation into and out of muscle. To clarify the transport mechanism of L-lactic acid in skeletal muscle, L-lactic acid uptake was investigated using a L6 cell line. mRNAs of monocarboxylate transporter (MCT) 1, 2 and 4 were found to be expressed in L6 cells. The [(14)C] L-lactic acid uptake by L6 cells increased up to pH of 6.0. The [(14)C] L-lactic acid uptake at pH 6.0 was concentration-dependent with a K(m) of 3.7 mM. This process was reduced by alpha-cyano-4-hydroxycinnamate, a typical MCT1, 2 and 4 inhibitor. These results suggest that an MCT participates in the uptake of L-lactic acid by L6 cells. [(14)C] L-lactic acid uptake was markedly inhibited by monocarboxylic acids and monocarboxylate drugs but not by dicarboxylic acids and amino acids. Moreover, benzoic acid, a substrate for MCT1, competitively inhibited this process with K(i) of 1.7 mM. [(14)C] L-lactic acid efflux in L6 cells was inhibited by alpha-cyano-4-hydroxycinnamate but not by benzoic acid. These results suggest that [(14)C] L-lactic acid efflux in L6 cells is mediated by MCT other than MCT1.