Characterization of an L-Carnitine Transport System in Murine Photoreceptor Cell Line

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  • Ohno Yuta
    Department of Pharmacology, Chiba University Graduate School of Medicine Department of Pharmacy, Gifu University Hospital
  • Otsuka Yusuke
    Department of Pharmacology, Chiba University Graduate School of Medicine
  • Nohara Masakatsu
    Department of Pharmacology, Chiba University Graduate School of Medicine
  • Furihata Tomomi
    Department of Pharmacology, Chiba University Graduate School of Medicine
  • Kuse Yoshiki
    Department of Biofunctional Evaluation, Gifu Pharmaceutical University
  • Itoh Yoshinori
    Department of Pharmacy, Gifu University Hospital
  • Hara Hideaki
    Department of Biofunctional Evaluation, Gifu Pharmaceutical University
  • Anzai Naohiko
    Department of Pharmacology, Chiba University Graduate School of Medicine

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<p>While it is well known that L-carnitine [3-hydroxy-4-(trimethylazaniumyl)-butanoate] is an essential molecule for β-oxidation, it provides anti-oxidative effects as well. Since these effects have been observed in photoreceptor cells, the carnitine’s intracellular concentration is considered to play a protective role against oxidative damage to those cells. However, even though its high hydrophilicity makes it likely that carnitine import is accomplished via a dedicated host transport system, the specific uptake process into those cells is currently unknown. Therefore, in this study, we sought to identify and characterize photoreceptor cell carnitine uptake transporter(s) utilizing 661W cells as a photoreceptor cell model. The results of our uptake assays showed that carnitine was transported into 661W cells in a saturable manner (Km=5.5 mM), and that the activity was susceptible to extracellular pH and Na+. While these data suggest the involvement of a transporter in 661W cell carnitine uptake, the observed transport profile did not correspond to any of the currently known carnitine transporters such as organic cation/carnitine transporter 1 (Octn1), Octn2, Octn3, B0,+ and Ct2. In fact, in our experiments, the mRNA expressions for such carnitine transporters in 661W cells were consistently very low and the carnitine transporter substrates did not inhibit the uptake activities. Taken as a whole, our results indicate that carnitine is transported into 661W cells in a carrier-mediated manner. However, since its transport modes cannot be fully explained by known carnitine transporters, it is highly likely that photoreceptor cells utilize a unique molecularly-based carnitine uptake system.</p>

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