Expression of monocarboxylic acid transporters (MCT) in brain cells

Mac, Magdalena; Nałęcz, Katarzyna A.

doi:10.1016/s0197-0186(03)00016-0

Cited by 25 publications

(9 citation statements)

References 36 publications

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“…The cellular distribution of MCT1 in the nervous system has been studied and described in more details. MCT1 was found to be expressed in the brain by endothelial cells [71] , [72] , [73] , astrocytes [74] , [75] , [76] , [77] , oligodendrocytes [78] , [79] and microglial cells [80] , [81] . In addition, some subsets of neurons express MCT1 [75] , [82] , [83] , notably in specific brain areas such as the hypothalamus [84] , [85] .…”

Section: General Description Of Monocarboxylate Transportersmentioning

confidence: 99%

Monocarboxylate transporters in the brain and in cancer

Pérez-Escuredo

Hée

Sboarina

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

315

289

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Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1–4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1–4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.

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Section: General Description Of Monocarboxylate Transportersmentioning

confidence: 99%

Monocarboxylate transporters in the brain and in cancer

Pérez-Escuredo

Hée

Sboarina

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

315

289

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“…In the CNS, MCT1 is widely expressed in oligodendrocytes (Rinholm et al, 2011; Lee et al, 2012), astrocytes (Broer et al, 1997; Leino et al, 1999; Hanu et al, 2000; Pierre et al, 2000), microglia (Moreira et al, 2009; Nijland et al, 2014), endothelial cells (Gerhart et al, 1997; Pellerin et al, 1998; Mac and Nalecz, 2003), and some specific neurons (Morrison et al, 2013; Perez-Escuredo et al, 2016). MCT1 is also expressed in tanycytes, a glial cell type found in the hypothalamus and this cell type is reported to produce lactate from glucose via glycolytic metabolism (Cortes-Campos et al, 2011).…”

Section: Monocarboxylate Transportersmentioning

confidence: 99%

“…The ANLSH depends on lactate being produced and released from astrocytes (via MCT1) and taken up by neurons (via MCT2) during times of neuronal activity (Pierre et al, 2000). MCT2 expression has also been seen in endothelial cells (Mac and Nalecz, 2003; BalmacedaAguilera et al, 2012), some rat astrocytes (Gerhart et al, 1998; Hanu et al, 2000), and tanycytes in the hypothalamus (Cortes-Campos et al, 2011). The expression of MCT3 is restricted to retinal pigmented epithelial cells (Yoon et al, 1997; Philp et al, 1998) and choroid plexus epithelium (Philp et al, 2001).…”

Section: Monocarboxylate Transportersmentioning

confidence: 99%

Glia-neuron energy metabolism in health and diseases: New insights into the role of nervous system metabolic transporters

Jha

Morrison

2018

Experimental Neurology

140

102

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The brain is, by weight, only 2% the volume of the body and yet it consumes about 20% of the total glucose, suggesting that the energy requirements of the brain are high and that glucose is the primary energy source for the nervous system. Due to this dependence on glucose, brain physiology critically depends on the tight regulation of glucose transport and its metabolism. Glucose transporters ensure efficient glucose uptake by neural cells and contribute to the physiology and pathology of the nervous system. Despite this, a growing body of evidence demonstrates that for the maintenance of several neuronal functions, lactate, rather than glucose, is the preferred energy metabolite in the nervous system. Monocarboxylate transporters play a crucial role in providing metabolic support to axons by functioning as the principal transporters for lactate in the nervous system. Monocarboxylate transporters are also critical for axonal myelination and regeneration. Most importantly, recent studies have demonstrated the central role of glial cells in brain energy metabolism. A close and regulated metabolic conversation between neurons and both astrocytes and oligodendroglia in the central nervous system, or Schwann cells in the peripheral nervous system, has recently been shown to be an important determinant of the metabolism and function of the nervous system. This article reviews the current understanding of the long existing controversies regarding energy substrate and utilization in the nervous system and discusses the role of metabolic transporters in health and diseases of the nervous system.

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“…MCT2 has also been found in the Purkinje fibers of the cerebellum as demonstrated by immunohistochemistry [84]. In brain endothelial cells, the presence of MCT2 was only observed in a few studies and thus this still needs to be further examined [82, 86]. Although MCT2 expression has been demonstrated in rodent brain, very little MCT2 expression was observed in human brain as shown by Northern blotting results [43].…”

Section: Localization Of Mcts In the Brainmentioning

confidence: 99%

Role of Monocarboxylate Transporters in Drug Delivery to the Brain

Vijay¹,

Morris²

2014

CPD

302

179

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Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors.

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Expression of monocarboxylic acid transporters (MCT) in brain cells

Cited by 25 publications

References 36 publications

Monocarboxylate transporters in the brain and in cancer

Monocarboxylate transporters in the brain and in cancer

Glia-neuron energy metabolism in health and diseases: New insights into the role of nervous system metabolic transporters

Role of Monocarboxylate Transporters in Drug Delivery to the Brain

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