Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1984217 | The International Journal of Biochemistry & Cell Biology | 2009 | 11 Pages |
Abstract
In the brain β-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 β-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 B0,+ 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 α (PPARα), 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. PPARα 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 PPARα 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.
Keywords
PBSOCTNDMEMSDSTRITCFITCGFAPGAPDHPPARαPPARBSADMSODulbecco's modified Eagle MediumWY-14,643Astrocytesbovine serum albuminDimethyl sulfoxidesodium dodecyl sulfatePhosphate buffered salinefluorescein isothiocyanatePeroxisomesGlial fibrillary acidic proteinCarnitineglyceraldehyde-3-phosphate dehydrogenase
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Authors
Elżbieta Januszewicz, Beata PajÄ
k, Barbara Gajkowska, Åukasz Samluk, Rouzanna L. Djavadian, Barry T. Hinton, Katarzyna A. NaÅÄcz,