Role of the monocarboxylate transporter MCT1 in the uptake of lactate during active recovery

Cupeiro, Rocío; Pérez-Prieto, Raúl; Amigo, Teresa; Gortázar, Pilar; Redondo, Carlos; González‐Lamuño, Domingo

doi:10.1007/s00421-016-3365-3

Cited by 22 publications

(26 citation statements)

References 29 publications

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“…Moreover, other pathways, such as AMPK pathways, were not studied in this research, but the regulation of NAD/NADH by the lactate metabolism may affect AMPK signaling independent of ROS to cause skeletal muscle adaptations [1]. Additionally, because lactate is a highly transportable molecule [14,28,29,30], it can travel to many tissues, such as the brain, liver, fat, and heart. Further research should be done to understand the role of exercise-produced lactate in tissues other than skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

N-acetyl-L-cysteine Prevents Lactate-Mediated PGC1-alpha Expression in C2C12 Myotubes

Nalbandian

Radák

Takeda

2019

Biology

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Background: Exercise induces many physiological adaptations. Recently, it has been proposed that some of these adaptations are induced by exercise-mediated lactate production. In this study, we aimed to investigate in vitro the effect of lactate in cultured myotubes and whether antioxidants could inhibit the effect. Methods: Differentiated myotubes were cultured at different concentrations of L-lactate (0, 10, 30, 50 mM) in the absence or presence of an antioxidant, N-acetyl-L-cysteine (Nac). The temporal effect of lactate exposure in myotubes was also explored. Results: Two hours of exposure to 50 mM L-lactate and six hours of exposure to 30 or 50 mM L-lactate caused a significant increase in PGC1-alpha (peroxisome proliferator-activated receptor γ coactivator-1α) expression in the myotubes. This up-regulation was suppressed by 2 mM Nac. Intermittent and continuous lactate exposure caused similar PGC1-alpha up-regulation. These results suggest that the increase in PGC1-alpha expression is mediated by reactive oxygen species (ROS) production from lactate metabolism and that both continuous and intermittent exposure to L-lactate can cause the up-regulation.

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Section: Discussionmentioning

confidence: 99%

N-acetyl-L-cysteine Prevents Lactate-Mediated PGC1-alpha Expression in C2C12 Myotubes

Nalbandian

Radák

Takeda

2019

Biology

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“…In support of this hypothesis, Ar-c155858, a specific MCT1 inhibitor, significantly reduced intracellular levels of d (−) lactic acid. MCT1 has previously been associated with uptake of this class of organic acid, rather than its extrusion, which is dependent on metabolism, cell type, and substrate concentrations between the extracellular and intracellular spaces ( 81 , 82 ). In monocytes, lactic acid uptake is dependent on MCT1, activating intracellular signaling involved in the expression of COX-2 ( 83 ).…”

Section: Discussionmentioning

confidence: 99%

d(−) Lactic Acid-Induced Adhesion of Bovine Neutrophils onto Endothelial Cells Is Dependent on Neutrophils Extracellular Traps Formation and CD11b Expression

et al. 2017

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Bovine ruminal acidosis is of economic importance as it contributes to reduced milk and meat production. This phenomenon is mainly attributed to an overload of highly fermentable carbohydrate, resulting in increased d(−) lactic acid levels in serum and plasma. Ruminal acidosis correlates with elevated acute phase proteins in blood, along with neutrophil activation and infiltration into various tissues leading to laminitis and aseptic polysynovitis. Previous studies in bovine neutrophils indicated that d(−) lactic acid decreased expression of L-selectin and increased expression of CD11b to concentrations higher than 6 mM, suggesting a potential role in neutrophil adhesion onto endothelia. The two aims of this study were to evaluate whether d(−) lactic acid influenced neutrophil and endothelial adhesion and to trigger neutrophil extracellular trap (NET) production (NETosis) in exposed neutrophils. Exposure of bovine neutrophils to 5 mM d(−) lactic acid elevated NET release compared to unstimulated neutrophil negative controls. Moreover, this NET contains CD11b and histone H4 citrullinated, the latter was dependent on PAD4 activation, a critical enzyme in DNA decondensation and NETosis. Furthermore, NET formation was dependent on d(−) lactic acid plasma membrane transport through monocarboxylate transporter 1 (MCT1). d(−) lactic acid enhanced neutrophil adhesion onto endothelial sheets as demonstrated by in vitro neutrophil adhesion assays under continuous physiological flow conditions, indicating that cell adhesion was a NET- and a CD11b/ICAM-1-dependent process. Finally, d(−) lactic acid was demonstrated for the first time to trigger NETosis in a PAD4- and MCT1-dependent manner. Thus, d(−) lactic acid-mediated neutrophil activation may contribute to neutrophil-derived pro-inflammatory processes, such as aseptic laminitis and/or polysynovitis in animals suffering acute ruminal acidosis.

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“…Importantly, both large payloads retained their organization, and neither acquired mutations during the engineering process. In addition, loading of the Hg MCT1 BAC clone introduced an allele of the Hg MCT1 locus (A1470T) associated with endurance and blood lactate levels after intensive exercise 12, 13, 26…”

Section: Discussionmentioning

confidence: 99%

Engineering Synthetic Chromosomes by Sequential Loading of Multiple Genomic Payloads over 100 Kilobase Pairs in Size

Greene¹,

Pascarelli²,

Broccoli³

et al. 2019

Molecular Therapy - Methods & Clinical Development

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Gene delivery vehicles currently in the clinic for treatment of monogenic disorders lack sufficient carrying capacity to efficiently address complex polygenic diseases. Thus, to engineer multifaceted genetic circuits for bioengineering human cells as a therapeutic option for polygenic diseases, we require new tools that are currently in their infancy. Mammalian artificial chromosomes, or synthetic chromosomes, represent a viable approach for delivery of large genetic payloads that are mitotically stable and remain independent of the host genome. Previously, we described a mammalian synthetic chromosome platform, termed the ACE system, that requires a single unidirectional integrase for the introduction of multiple genes onto the ACE platform chromosome. In this report, we provide a proof of concept that the ACE synthetic chromosome bioengineering platform is amenable to sequential delivery of off-the-shelf large genomic fragments. Specifically, large genomic clones spanning the human solute carrier family 2, facilitated glucose transporter member 1 ( SLC2A1 or GLUT1 , 169 kbp), and human monocarboxylate transporter 1 ( SLC16A1 or MCT1 , 144 kbp) genetic loci were engineered onto the ACE platform and demonstrated to express and correctly splice both gene transcripts. Thus, the ACE system provides a facile and tractable engineering platform for the development of gene-based therapeutic agents targeting polygenic diseases.

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Role of the monocarboxylate transporter MCT1 in the uptake of lactate during active recovery

Abstract: These differences according to the polymorphic variant T1470A suggest that MCT1 affects the plasma lactate decrease during a crucial period of active recovery, where the maximal lactate amount is cleared (i.e. 10-20 min period).

Cited by 22 publications

References 29 publications

N-acetyl-L-cysteine Prevents Lactate-Mediated PGC1-alpha Expression in C2C12 Myotubes

N-acetyl-L-cysteine Prevents Lactate-Mediated PGC1-alpha Expression in C2C12 Myotubes

d(−) Lactic Acid-Induced Adhesion of Bovine Neutrophils onto Endothelial Cells Is Dependent on Neutrophils Extracellular Traps Formation and CD11b Expression

Engineering Synthetic Chromosomes by Sequential Loading of Multiple Genomic Payloads over 100 Kilobase Pairs in Size

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