Functional activity of L-carnitine transporters in human airway epithelial cells
| Autor: | Amelia Barilli, Rossana Visigalli, Paola Puccini, Valeria Dall'Asta, Benedetta Riccardi, Filippo Ingoglia, Bianca Maria Rotoli |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Arginine Amino Acid Transport Systems Organic Cation Transport Proteins Biophysics Biological Transport Active Respiratory Mucosa SLC22A5 Biochemistry Carnitine transport 03 medical and health sciences 0302 clinical medicine Carnitine Cell Line Tumor medicine Humans Inner mitochondrial membrane Solute Carrier Family 22 Member 5 chemistry.chemical_classification Organic cation transport proteins biology Symporters Transporter Epithelial Cells Cell Biology Amino acid 030104 developmental biology Amino Acid Transport Systems Neutral chemistry Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein medicine.drug |
| Zdroj: | Biochimica et biophysica acta. 1858(2) |
| ISSN: | 0006-3002 |
| Popis: | Carnitine plays a physiologically important role in the β-oxidation of fatty acids, facilitating the transport of long-chain fatty acids across the inner mitochondrial membrane. Distribution of carnitine within the body tissues is mainly performed by novel organic cation transporter (OCTN) family, including the isoforms OCTN1 (SLC22A4) and OCTN2 (SLC22A5) expressed in human. We performed here a characterization of carnitine transport in human airway epithelial cells A549, Calu-3, NCl-H441, and BEAS-2B, by means of an integrated approach combining data of mRNA/protein expression with the kinetic and inhibition analyses of L-[(3)H]carnitine transport. Carnitine uptake was strictly Na(+)-dependent in all cell models. In A549 and BEAS-2B cells, carnitine uptake was mediated by one high-affinity component (Km2 μM) identifiable with OCTN2. In both these cell models, indeed, carnitine uptake was maximally inhibited by betaine and strongly reduced by SLC22A5/OCTN2 silencing. Conversely, Calu-3 and NCl-H441 exhibited both a high (Km~20 μM) and a low affinity (Km1 mM) transport component. While the high affinity component is identifiable with OCTN2, the low affinity uptake is mediated by ATB(0,+), a Na(+), and Cl(-)-coupled transport system for neutral and cationic amino acids, as demonstrated by the inhibition by leucine and arginine, as well as by SLC6A14/ATB(0,+) silencing. The presence of this transporter leads to a massive accumulation of carnitine inside the cells and may be of peculiar relevance in pathologic conditions of carnitine deficiency, such as those associated to OCTN2 defects. |
| Databáze: | OpenAIRE |
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