Expression of monocarboxylic acid transporters (MCT) in brain cells. Implication for branched chain alpha-ketoacids transport in neurons.
The alpha-ketoisocaproic acid (KIC) is a short branched-chain monocarboxylate, which accumulates in neural cells. It plays an important role in maintaining nitrogen balance in the brain, a process of a great importance for shuttling of glutamine and glutamate between astrocytes and neurons. Higher accumulation of KIC in isolated cerebral cortex neurons at lower external pH, as well as sensitivity of this process to alpha-cyano-4-hydroxycinnamate indicate an involvement of a transporter, belonging to the family of monocarboxylate transporters (MCT).The expression of MCT1 and MCT2 isoforms in the brain cells was studied using reverse transcriptase-polymerase chain reaction (RT-PCR) method. 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. MCT2, which is less abundant isoform than MCT1, was expressed in astrocytes, in brain endothelial cells and at low level in newborn rats' neurons, being absent in neurons from adult brain.The observed sensitivity of KIC accumulation towards SH-groups reagents did not fit to the known characteristics of MCT1 and MCT2. Therefore, the change of MCT expression during brain development, as well as lack of MCT1 and MCT2 in neurons of adults, point to another MCT isoform being involved in alpha-ketoisocaproic acid accumulation. This could be either one of other known MCT isoforms or a new member of family MCT, specific towards branched chain alpha-ketoacids.
Mac
Magdalena
M
Nencki Institute of Experimental Biology, Department of Molecular and Cellular Neurobiology, 3 Pasteur Street, 02-093 Warszawa, Poland.
Nałecz
Katarzyna A
KA
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D017931:DNA Primers; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger