Search results for "Lactate transport"
showing 5 items of 5 documents
Lactate as a Metabolite and a Regulator in the Central Nervous System
2016
More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even invol…
Abstract 5476: Inhibiting lactate transporters MCT-1 and MCT-4 target hypoxic HNSCC cells and sensitize them to metformin
2018
Abstract Head and neck squamous cell carcinoma (HNSCC) is treated primarily through a combination of surgery and radiation therapy. The problem of radioresistance, however, persists and requires new approaches to overcome it. Tumor hypoxia has been shown to be a driver of radioresistance, thereby prompting the targeting of the hypoxic niche, known to be highly glycolytic. Two key components of the hypoxic metabolic profile are lactate transporters MCT-1 and MCT-4, which sustain hypoxia-driven lactate production in cells. We hypothesize that inhibition of MCT-1 and MCT-4 will selectively target the growth of hypoxic tumor cells and potentially exert a synergistic effect with the antidiabetic…
The role of NG2 and OPC in induction and development of CNS inflammation
2014
encephalitis (EAE) mouse models (J Neurosci 31:669, 2011; Brain 136:1760, 2013). Further, it has been shown that in addition to infiltrating leukocytes, astrocytes and microglia also exhibit high expression of EMMPRIN in diseased brain. EMMPRIN has been reported to interact with monocarboxylate transporter-1 (MCT-1) in astrocytes; the lattermediates lactate transport to neurons. Given that perturbation in energymetabolism can have catastrophic effects on homeostasis of the brain, it is paramount to understand EMMPRIN expression in astrocytes in normal andMS brain.We have used human fetal astrocytes (HFA) and determined their EMMPRIN levels by flow cytometry and microscopy. We found that HFA…
Inhibition of lactate export by quercetin acidifies rat glial cells in vitro
1997
The relationship between glial lactate release and glial intracellular pH (pH i) regulation is studied using C6 glioma cells and rat astrocytes in vitro, and the lactate transport inhibitors quercetin and a-cyano-4-hydroxycinnamate (CHC). pHi is measured using 2′,7′bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). The results show that lactate release is mediated partly by a specific lactate transport system inhibitable by quercetin (50 mM), but not by CHC (5 mM). Inhibition by quercetin results in a significant 3‐4-fold increase of intracellular lactate and a decrease of intracellular pH to 6.9. A participation of quercetin-inhibitable lactate transport in glial pHi-regulation is suggested…
Exercise and lactate production:implication in fatigue and in brain signaling
2016
More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even invol…