Evidence for creatine biosynthesis in Müller glia

Authors

  • Toshihisa Nakashima,

    1. Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan
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  • Masatoshi Tomi,

    1. Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan
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  • Masanori Tachikawa,

    1. Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
    Current affiliation:
    1. Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan
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  • Masahiko Watanabe,

    1. Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan
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  • Tetsuya Terasaki,

    1. Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
    2. New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan
    3. SORST of the Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan
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  • Ken-ichi Hosoya

    Corresponding author
    1. Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan
    • Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
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Abstract

In high-energy metabolic tissues like the retina, creatine may play an important role in energy storage and in transmission of phosphate-bound energy substrates. To prove this, we investigated creatine synthesis in Müller glia. We also characterized the localization of the creatine synthetic enzyme, S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT) in the retina. Reverse transcription-polymerase chain reaction analysis revealed that L-arginine:glycine amidinotransferase and GAMT mRNAs were expressed in the retina and the Müller cell line, TR-MUL5. [14C]Creatine was detected after incubation of isolated rat retina or TR-MUL5 cells with [14C]glycine, L-arginine and L-methionine, suggesting creatine synthesis in Müller glia. Western blot analysis also revealed expression of GAMT protein in the rat retina and TR-MUL5 cells. Furthermore, confocal immunofluorescent microscopy of dual-labeled rat retinal sections demonstrated co-localization of GAMT with glutamine synthetase. Taken together, the results of the present study indicate creatine synthesis in Müller glia, implying an important role of creatine in energy metabolism in the retina. © 2005 Wiley-Liss, Inc.

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