Disease relevance of SLC16A4

• Expression of MCT1 and MCT4 in a patient with mitochondrial myopathy [1].
• MCT1 and MCT4 were expressed in BM vesicles, but there was no difference in expression between the IUGR and AGA groups [2].

High impact information on SLC16A4

• Monocarboxylate transporters MCT1-MCT4 require basigin (CD147) or embigin (gp70), ancillary proteins with a glutamate residue in their single transmembrane (TM) domain, for plasma membrane (PM) expression and activity [3].
• In the heart, the testosterone-induced increase in lactate transport cannot be explained by changes in plasmalemmal MCT1 content, but in skeletal muscle the increase in the rate of lactate transport was associated with increases in plasmalemmal MCT1 and MCT4 [4].
• Testosterone increases lactate transport, monocarboxylate transporter (MCT) 1 and MCT4 in rat skeletal muscle [4].
• In contrast, there was a strong positive relationship between the testosterone-induced increments in MCT4 protein and the fast-twitch fibre composition of rat muscles [4].
• We have examined the effects of administration of testosterone for 7 days on monocarboxylate transporter (MCT) 1 and MCT4 mRNAs and proteins in seven metabolically heterogeneous rat hindlimb muscles and in the heart [4].

Biological context of SLC16A4

• In intact rat skeletal muscle fibers from the flexor digitorum brevis muscle, the simvastatin-induced alteration of Ca2+ homeostasis is abolished when monocarboxylate transporter (MCT4) is inhibited [5].
• We determined the effect of 20 nights of live high, train low (LHTL) hypoxic exposure on lactate kinetics, monocarboxylate lactate transporter proteins (MCT1 and MCT4), and muscle in vitro buffering capacity (betam) in 29 well-trained cyclists and triathletes [6].
• This study demonstrates that sprint training of this length and type results in an upregulation of MCT1 protein, but not MCT4 content [7].
• These genes are of special interest, because their products have important roles in cellular glucose metabolism, from glucose uptake (GLUT1) to glycolysis (PFKP) and lactate export (MCT4) [8].

Anatomical context of SLC16A4

• Immunohistochemical studies confirmed that human MCT1 antibody labeling was confined to the apical membranes, whereas MCT5 antibody staining was restricted to the basolateral membranes of the colonocytes [9].
• Lactate is released from skeletal muscle in proportion to glucose uptake rates, and it leaves the cells via simple diffusion and two monocarboxylate transporter proteins, MCT1 and MCT4 [10].
• MCT4 expression appears to be specific for astrocytes [11].
• In addition, we also examined the effects of testosterone treatment on plasmalemmal MCT1 and MCT4, and lactate transport into giant sarcolemmal vesicles prepared from red and white hindlimb muscles and the heart [4].
• To evaluate the effects of endurance training on the expression of monocarboxylate transporters (MCT) in human vastus lateralis muscle, we compared the amounts of MCT1 and MCT4 in total muscle preparations (MU) and sarcolemma-enriched (SL) and mitochondria-enriched (MI) fractions before and after training [12].

Associations of SLC16A4 with chemical compounds

• Effects of strength training on muscle lactate release and MCT1 and MCT4 content in healthy and type 2 diabetic humans [10].
• Accordingly, MCT2 or MCT4 is responsible for L-lactic acid efflux by RD cells [13].
• MCT1 and MCT4 contents were quantified by Western blots, and maximal muscle oxidative capacity (V(max)) was evaluated with pyruvate + malate and glutamate + malate as substrates [14].
• These results suggest that the carrier-mediated transport system is involved in the uptake of telmisartan by Caco-2 cells and that the apical-localized transport system is similar to MCTs, but not MCT1-MCT4 [15].
• K0.5 values of MCT4 (determined at 30 mM L-lactate) for inhibition by alpha-cyano-4-hydroxycinnamate (991 microM), phloretin (41 microM), 5-nitro-2-(3-phenylpropylamino)benzoate (240 microM), p-chloromercuribenzene sulphonate (21 microM) and 3-isobutyl-1-methylxanthine (970 microM, partial inhibition) were also substantially higher than for MCT1 [16].

Analytical, diagnostic and therapeutic context of SLC16A4

• The Western blotting revealed a positive, linear relationship between the MCT1 content and the occurrence of type I fibers in the muscle, but no significant relation was found between MCT4 content and fiber type [17].
• The immunofluorescence microscopy showed that within a given muscle section, the MCT4 isoform was clearly more abundant in type II fibers than in type I fibers, whereas only minor differences existed in the occurrence of the MCT1 isoform between type I and II fibers [17].
• ELISA indicated the expression of only MCT1, MCT4, and MCT8 isoforms by ARPE-19 cells [18].

References