Disease relevance of Slc16a1

• MCT1 function and regulation have not been characterized previously in cerebral endothelial cells but may be important during normal cerebral energy metabolism and during brain diseases such as stroke [1].
• The mRNA coding MCT1 was detected in astrocytes, brain endothelial cells, tumour cells (neuroblastoma and glioma) and in cortex neurons of newborn rats, but not in adult ones [2].
• Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after long-term hypobaric hypoxia [3].
• We examined the hypothesis that vagal complex monocarboxylate transporter protein levels are gender dependent and estrogen dependent, and that estrogen influences adaptation of these protein responses during repeated insulin-induced hypoglycemia [4].
• It follows that the increased transmembrane flux of lactate during exercise or in pathological conditions such as ischemia must be a result of altered substrate gradients rather than of translocation of MCT1 molecules to the plasma membrane [5].

High impact information on Slc16a1

• Adenovirus-mediated overexpression of MCT-1 increased lactate transport activity 3.7-fold in INS-1 cells [6].
• Adenovirus-mediated overexpression of MCT-1 caused an increase in pyruvate oxidation and conferred pyruvate-stimulated insulin release to isolated rat islets [6].
• In this study the significance of these characteristics was explored by overexpressing type A LDH (LDH-A) and/or type 1 MCT (MCT-1) in the clonal INS-1 beta cells and isolated rat islets [6].
• The data demonstrate the direct modulation of MCT1 kinetic function in cerebral endothelial cells by agents known to affect the beta-adrenergic receptor/adenylyl cyclase/cAMP/protein kinase A intracellular signaling pathway [1].
• MCT1-independent intracellular pH control mechanisms did not contribute to the forskolin or H89 effects on MCT1 kinetic function as determined with amiloride, monocarboxylate-independent acid loading, or the transport inhibitor alpha-cyano-4-hydroxycinnamate [1].

Chemical compound and disease context of Slc16a1

• This study used the rat hippocampal slice preparation and the monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), to assess the obligatory role that lactate plays in fueling the recovery of synaptic function after hypoxia upon reoxygenation [7].
• Caudal fourth ventricular (CV4) infusion of the monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamic acid (4CIN), causes hyperglycemia coincident with Fos expression in the hindbrain nucleus tractus solitarius, a rare central source of metabolic deficit signaling [8].

Biological context of Slc16a1

• By immunogold cytochemistry, it could be demonstrated that the MCT2 immunosignal was concentrated at postsynaptic densities of parallel fiber-Purkinje cell synapses [9].
• The expression of MCT2 in synaptic membranes may allow energy supply to be tuned to the excitatory drive [9].
• Transport kinetics were similar, but not identical, to those determined using the same technique for the monocarboxylate transporter (MCT) of Ehrlich Lettré tumor cells (MCT1) (Carpenter, L., and Halestrap, A. P. (1994) Biochem. J. 304, 751-760) [10].
• Resting T cells did not induce a relevant upregulation of MCT1 in astrocytes [11].
• Interaction with antigen-specific T cells regulates expression of the lactate transporter MCT1 in primary rat astrocytes: specific link between immunity and homeostasis [11].

Anatomical context of Slc16a1

• MCT1 was cloned and expressed in Xenopus laevis oocytes [12].
• The luminal and abluminal endothelial plasma membranes in retina also exhibited heavy labeling by antibody to monocarboxylate transporter-1 [13].
• Monocarboxylate transporter-1 was most highly expressed by the apical processes of retinal pigment epithelium that surround the outer segments of the photoreceptor cells [13].
• In contrast to glucose transporter-1, monocarboxylate transporter-1 was not detected on the basal membranes of pigment epithelium [13].
• These results provide biochemical evidence of a H(+)-coupled and saturable transport system, presumed to be a low-affinity monocarboxylate transporter MCT4 or other unknown H(+)-coupled monocarboxylate transport system, for nicotinate in rat cerebrocortical astrocytes [14].

Associations of Slc16a1 with chemical compounds

• Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons [12].
• Furthermore, the cellular uptake of benzoic acid, a representative substrate of MCT1, was significantly (p<0.05) enhanced following the activation of IGF-IR via the pre-incubation with IGF-I (10 ng/ml) [15].
• This process was reduced by a protonophore, carbonylcyanide p-trifluoromethoxyphenylhydrazone, and a typical monocarboxylate transporter (MCT) inhibitor, alpha-cyano-4-hydroxycinnamic acid, suggesting that nicotinate uptake by rat astrocytes is mediated by H(+)-coupled monocarboxylate transport system [14].
• The distribution of MCT2 transporters within the individual postsynaptic densities mimicked that of the delta2 glutamate receptor, as shown by use of two different gold-particle sizes [9].
• Differences in stereoselectivity were also detected; both carriers showed a lower Km for L-lactate than D-lactate, while hepatocyte MCT exhibited a lower Km for D- than L-2-chloropropionate and for L- than D-3-hydroxybutyrate; this is not the case for MCT1 [10].

Other interactions of Slc16a1

• Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina [13].
• The objective was to further test the hypothesis that aluminum (Al) citrate transport across the blood-brain barrier is mediated by a monocarboxylate transporter (MCT) [16].
• Induction of Fos immunoreactivity labeling in rat forebrain metabolic loci by caudal fourth ventricular infusion of the monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamic acid [8].
• A significant reduction in type I myosin heavy chain (MHC) in the soleus and a strong trend (P = 0.06) for a reduced type IIx MHC in the plantaris were observed in MVO rats, but no differences in citrate synthase activity or monocarboxylate transporter proteins (MCT)-1 expression were noted in any muscle [17].

Analytical, diagnostic and therapeutic context of Slc16a1

• Using reverse transcriptase-polymerase chain reaction and Northern blotting, the presence of mRNA coding for the monocarboxylate transporter 1 (MCT1) was demonstrated in primary cultures of astroglial cells [12].
• Confocal immunofluorescence microscopy showed strong monocarboxylate transporter 2 (MCT2) labeling of Purkinje cell bodies and punctate labeling in the molecular layer [9].
• MCT1 activity was assessed by changes of intracellular H+ concentration measured by pH-selective microelectrodes during application of lactate [18].
• Starvation of rats for up to 48 h did not lead to any change in MCT1 or MCT2 expression in the liver, as determined by either Northern or Western blotting [19].
• Reverse transcription-polymerase chain reaction (RT-PCR) indeed disclosed the expression of MCT1 and MCT2 in both GLUT1 and LacZ cells [20].

References