Monocarboxylate transport in erythrocytes

Deüticke, B.

doi:10.1007/bf01870219

Cited by 186 publications

(176 citation statements)

References 91 publications

(151 reference statements)

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“…Although being the most commonly used MCT1 inhibitor, CHC has also been described as a potent inhibitor of the mitochondrial pyruvate transporter (Halestrap & Denton 1974); however, permeability studies carried out by others show that CHC is not internalised by U-87MG glioma cells (Colen et al 2006). Additionally, CHC has also been identified as an inhibitor of the anion exchanger 1 (Deuticke 1982), an important pH regulator that is responsible for Cl K /HCO 3 K membrane exchange (Kopito 1990). Different effects have been identified as mediating the antitumour activity of quercetin, including cell cycle arrest (Yang et al 2006) and apoptosis (Granado-Serrano et al 2006, Yang et al 2006, as well as inhibition of the phosphatidylinositol 3-kinase/Akt pathway Granado-Serrano et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Over recent years, different approaches have been used to inhibit lactate efflux from cancer cells, including MCT small-molecule inhibitors such as a-cyano-4-hydroxycinnamic acid (CHC; Colen et al 2006, Sonveaux et al 2008, lonidamine (Ben-Horin et al 1995, Ben-Yoseph et al 1998, Fang et al 2006, flavonoids such as quercetin (Belt et al 1979, Deuticke 1982, Wang & Morris 2007, and MCT siRNA (Mathupala et al 2004, Fang et al 2006, Sonveaux et al 2008. The inhibition of MCTs has a direct effect on lactate transport, as well as on pH homeostasis, therefore having an important effect on cancer cell viability.…”

Section: Introductionmentioning

confidence: 99%

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Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Morais-Santos¹,

Miranda-Gonçalves²,

Pinheiro³

et al. 2013

Endocrine-Related Cancer

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The tumour microenvironment is known to be acidic due to high glycolytic rates of tumour cells. Monocarboxylate transporters (MCTs) play a role in extracellular acidification, which is widely known to be involved in tumour progression. Recently, we have described the upregulation of MCT1 in breast carcinomas and its association with poor prognostic variables. Thus, we aimed to evaluate the effect of lactate transport inhibition in human breast cancer cell lines. The effects of a-cyano-4-hydroxycinnamate, quercetin and lonidamine on cell viability, metabolism, proliferation, apoptosis, migration and invasion were assessed in a panel of different breast cancer cell lines. MCT1, MCT4 and CD147 were differently expressed among the breast cancer cell lines and, as expected, different sensitivities were observed for the three inhibitors. Interestingly, in the most sensitive cell lines, lactate transport inhibition induced a decrease in cell proliferation, migration and invasion, as well as an increase in cell death. Results were validated by silencing MCT1 expression using siRNA. The results obtained here support targeting of lactate transport as a strategy to treat breast cancer, with a special emphasis on the basal-like subtype, which so far does not have a specific molecular therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Morais-Santos¹,

Miranda-Gonçalves²,

Pinheiro³

et al. 2013

Endocrine-Related Cancer

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“…The accumulation of lactate and hydrogen ions in muscle during exercise may inhibit muscular function and cause fatigue (13,16). High-RBC uptake of these ions could help in establishing a gradient between plasma and interstitial fluid (9,28). Transport of these metabolites away from the exercising muscles into the blood would reduce the potential for muscle acidosis and delay the onset of fatigue.…”

Section: Lactate Influxmentioning

confidence: 99%

Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?

Connes¹,

Bouix²,

Py³

et al. 2004

Journal of Applied Physiology

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. Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes? J Appl Physiol 97: 1053-1058. First published April 30, 2004 10.1152/japplphysiol.00993.2003.-This study investigated 1) red blood cells (RBC) rigidity and 2) lactate influxes into RBCs in endurance-trained athletes with and without exercise-induced hypoxemia (EIH). Nine EIH and six non-EIH subjects performed a submaximal steady-state exercise on a cycloergometer at 60% of maximal aerobic power for 10 min, followed by 15 min at 85% of maximal aerobic power. At rest and at the end of exercise, arterialized blood was sampled for analysis of arterialized pressure in oxygen, and venous blood was drawn for analysis of plasma lactate concentrations and hemorheological parameters. Lactate influxes into RBCs were measured at three labeled [U-14 C]lactate concentrations (1.6, 8.1, and 41 mM) on venous blood sampled at rest. The EIH subjects had higher maximal oxygen uptake than non-EIH (P Ͻ 0.05). Total lactate influx was significantly higher in RBCs from EIH compared with non-EIH subjects at 8.1 mM (1,498.1 Ϯ 87.8 vs. 1,035.9 Ϯ 114.8 nmol ⅐ ml Ϫ1 ⅐ min Ϫ1 ; P Ͻ 0.05) and 41 mM (2,562.0 Ϯ 145.0 vs. 1,618.1 Ϯ 149.4 nmol ⅐ ml Ϫ1 ⅐ min Ϫ1 ; P Ͻ 0.01). Monocarboxylate transporter-1-mediated lactate influx was also higher in EIH at 8.1 mM (P Ͻ 0.05) and 41 mM (P Ͻ 0.01). The drop in arterial oxygen partial pressure was negatively correlated with total lactate influx measured at 8.1 mM (r ϭ Ϫ0.82, P Ͻ 0.05) and 41 mM (r ϭ Ϫ0.84, P Ͻ 0.05) in the two groups together. Plasma lactate concentrations and hemorheological data were similar in the two groups at rest and at the end of exercise. The results showed higher monocarboxylate transporter-1-mediated lactate influx in the EIH subjects and suggested that EIH could modify lactate influx into erythrocyte. However, higher lactate influx in EIH subjects was not accompanied by an increase in RBC rigidity. monocarboxylate transporter; endurance; lactate metabolism; hypoxemia; hemorheology TRANSPORT OF LACTATE ACROSS the erythrocyte membrane proceeds by three distinct pathways (9): 1) nonionic diffusion of the undissociated acid; 2) an inorganic anion-exchange system, often referred to as the band 3 system; and 3) a monocarboxylate-specific carrier mechanism (23). Juel et al. (18) recently showed that monocarboxylate transporter-1 (MCT-1) and band 3 expressions were increased with chronic hypoxia exposure, suggesting that these proteins may be upregulated by hypoxia.The functional significance of the hypoxia-induced changes is likely an increase of lactate and H ϩ fluxes from plasma to erythrocyte. During sea-level exercise, some endurance-trained athletes experience arterial hypoxemia [exercise-induced hypoxemia (EIH)] that can be defined as a decrease in both oxygen arterial partial pressure (Pa O 2 ) and arterial hemoglobin saturation during exercise (8). Miyachi and Katayama (21) have reported repeated episodes of EIH during training sessions when endurance athlet...

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“…The most extensively studied MCT is that found in the red blood cell (Deuticke, 1982;Poole and Halestrap, 1993), which has been identified and partially purified in this laboratory (Poole and Halestrap, 1992). N-terminal sequencing (Poole and Halestrap, 1994) has shown it to be the same as the transporter recently cloned and sequenced from Chinese hamster ovary cells and named MCT1 (Garcia et al, 1994).…”

mentioning

confidence: 99%

The Kinetics, Substrate, and Inhibitor Specificity of the Monocarboxylate (Lactate) Transporter of Rat Liver Cells Determined Using the Fluorescent Intracellular pH Indicator, 2′,7′-Bis(carboxyethyl)-5(6)-carboxyfluorescein

Jackson¹,

Halestrap

1996

Journal of Biological Chemistry

173

129

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The kinetics of transport of L-lactate, pyruvate, ketone bodies, and other monocarboxylates into isolated hepatocytes from starved rats were measured at 25°C using the intracellular pH-sensitive dye, 2 ,7 -bis(carboxyethyl)-5(6)-carboxyfluorescein, to detect the associated proton influx. Transport kinetics were similar, but not identical, to those determined using the same technique for the monocarboxylate transporter (

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Monocarboxylate transport in erythrocytes

Abstract: Key words Erythrocyte membrane 9 monocarboxylate transport 9 co-transport -nonionic diffusion.

Cited by 186 publications

References 91 publications

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?

The Kinetics, Substrate, and Inhibitor Specificity of the Monocarboxylate (Lactate) Transporter of Rat Liver Cells Determined Using the Fluorescent Intracellular pH Indicator, 2′,7′-Bis(carboxyethyl)-5(6)-carboxyfluorescein

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