title: Organic cation/carnitine transporter OCTN3 is present in astrocytes and is up-regulated by peroxisome proliferators-activator receptor agonist.
abstract: 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.
authors.affiliation: Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Januszewicz
authors.forename: Beata
authors.initials: B
authors.lastname: Pajak
authors.forename: Barbara
authors.initials: B
authors.lastname: Gajkowska
authors.forename: Lukasz
authors.initials: L
authors.lastname: Samluk
authors.forename: Rouzanna L
authors.initials: RL
authors.lastname: Djavadian
authors.forename: Barry T
authors.initials: BT
authors.lastname: Hinton
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Nałecz
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002331:Carnitine / Q000378:metabolism; D008854:Microscopy, Electron; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D047493:PPAR alpha / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000494:pharmacology; D020675:Peroxisomes / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C549957:LOC303140 protein, rat; D027701:Organic Cation Transport Proteins; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; C006253:pirinixic acid; D002331:Carnitine