In the brain beta-oxidation, which takes place in astrocytes, is not a major process
of energy supply. Astrocytes synthesize important lipid metabolites, mainly due to
the processes taking place in peroxisomes. One of the compounds necessary in the process
of mitochondrial beta-oxidation and export of acyl moieties from peroxisomes is l-carnitine.
Two Na-dependent plasma membrane carnitine transporters were shown previously to be
present in astrocytes: a low affinity amino acid transporter B(0,+) and a high affinity
cation/carnitine transporter OCTN2. The expression of OCTN2 is known to increase in
peripheral tissues upon the stimulation of peroxisome proliferators-activator receptor
alpha (PPARalpha), a nuclear receptor known to up-regulate several enzymes involved
in fatty acid metabolism. The present study was focused on another high affinity carnitine
transporter-OCTN3, its presence, regulation and activity in astrocytes. Experiments
using the techniques of real-time PCR, Western blot and immunocytochemistry analysis
demonstrated the expression of octn3 in rat astrocytes and, out of two rat sequences
ascribed as similar to mouse OCTN3, XM_001073573 was found in these cells. PPARalpha
activator-2-[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid
(WY-14,643) stimulated by 50% expression of octn3, while, on the contrary to peripheral
tissues, it did not change the expression of octn2. This observation was correlated
with an increased Na-independent activity of carnitine transport. Analysis by transmission
electron microscopy showed an augmented intracellular localization of OCTN3 upon PPARalpha
stimulation, mainly in peroxisomes, indicating a physiological role of OCTN3 as peroxisomal
membrane transporter. These observations point to an important role of OCTN3 in peroxisomal
fatty acid metabolism in astrocytes.