Demonstration of kynurenine aminotransferases I and II and characterization of kynurenic acid synthesis in oligodendrocyte cell line (OLN-93).

In the present study we demonstrate for the first time that both kynurenine aminotransferase (KAT) isoforms I and II are present in the permanent immature rat oligodendrocytes cell line (OLN-93). Moreover, we provide evidence that OLN-93 cells are able to synthesize kynurenic acid (KYNA) from exogenously added L-kynurenine and we characterize its regulation by extrinsic factors. KYNA production in OLN-93 cells was depressed in the presence of aminotransferase inhibitor, aminooxyacetic acid and was not affected by depolarizing agents such as 50 mM K+ and 4-aminopyridine. Glutamate agonists, L-glutamate and D,L-homocysteine significantly decreased KYNA production. Selective agonist of ionotropic glutamate receptors Amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropionic acid (AMPA) lowered KYNA production in OLN-93 cell line, whereas N-methyl-D-aspartate (NMDA) had no influence on KYNA production. Furthermore, KYNA synthesis in OLN-93 cells was decreased in a concentration-dependent manner by amino acids transported by L-system, L-leucine, L-cysteine and L-tryptophan. The role of KYNA synthesis in oligodendrocytes needs further investigation.