Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle

Abstract

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. To determine if changes in muscle lactate release and oxidation were associated with training-induced changes in MCT expression, we correlated band densities in Western blots to lactate kinetics determined in vivo. Nine weeks of leg cycle endurance training [75% peak oxygen consumption (VO(2 peak))] increased muscle citrate synthase activity (+75%, P < 0.05) and percentage of type I myosin heavy chain (+50%, P < 0.05); percentage of MU lactate dehydrogenase-5 (M4) isozyme decreased (-12%, P < 0.05). MCT1 was detected in SL and MI fractions, and MCT4 was localized to the SL. Muscle MCT1 contents were consistent among subjects both before and after training; in contrast, MCT4 contents showed large interindividual variations. MCT1 amounts significantly increased in MU, SL, and MI after training (+90%, +60%, and +78%, respectively), whereas SL but not MU MCT4 content increased after training (+47%, P < 0.05). Mitochondrial MCT1 content was negatively correlated to net leg lactate release at rest (r = -0.85, P < 0.02). Sarcolemmal MCT1 and MCT4 contents correlated positively to net leg lactate release at 5 min of exercise at 65% VO(2 peak) (r = 0.76, P < 0.03 and r = 0. 86, P < 0.01, respectively). Results support the conclusions that 1) endurance training increases expression of MCT1 in muscle because of insertion of MCT1 into both sarcolemmal and mitochondrial membranes, 2) training has variable effects on sarcolemmal MCT4, and 3) both MCT1 and MCT4 participate in the cell-cell lactate shuttle, whereas MCT1 facilitates operation of the intracellular lactate shuttle.

Expression and Distribution of Lactate/Monocarboxylate Transporter Isoforms in Pancreatic Islets and the Exocrine Pancreas

“…In contrast, MCT1 was expressed strongly at the plasma membrane of acinar cells, but no staining of intracellular membranes was apparent. These data argue against a mitochondrial location of MCT1, contrary to the proposal of others (30). Indeed, we have not detected any MCT1 associated with mitochondria in any cell type or in isolated mitochondrial preparations (M.W., A.P.H., unpublished data).…”

Physical and Functional Association of Lactate Dehydrogenase (LDH) with Skeletal Muscle Mitochondria

“…Several previous studies lent support for the direct uptake and oxidation of lactate by the mitochondria (19,23,27,28), as per the intracellular lactate shuttle hypothesis (ILSH). The ILSH postulates that lactate can be directly transported into the mitochondria where it is oxidized, to fuel respiration (1).…”

Influence of Acqua Lete® (Bicarbonate Calcic Natural Mineral Water) Hydration on Blood Lactate After Exercise

“…The intracellular lactate shuttle (ILS) hypothesis holds that lactate produced as the result of glycolysis and glycogenolysis in the cytosol, is balanced by oxidative removal in mitochondria of the same cell. The presence of intracellular lactate shuttles gives rise to the notion that glycolytic and oxidative pathways can be viewed as linked processes, because lactate, the product of one pathway, is the substrate for the other [30]. After its continuous production in citosol by LDH5 (M4), lactate diffusing in mitochondrial matrix, where LDH1 (H4) would catalyse the conversion of lactate back to pyruvate, with concomitant interconversion of NADH and NAD.…”