Expression and regulation of L-cystine transporter, system X c-, in the newly developed rat retinal Müller cell line (TR-MUL)

Masatoshi Tomi, Takeshi Funaki, Hayato Abukawa, Kazunori Katayama, Tetsu Kondo, Sumio Ohtsuki, Masatsugu Ueda, Masuo Obinata, Tetsuya Terasaki, Ken Ichi Hosoya

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80 Citations (Scopus)


The purpose of the present study was to elucidate the expression and regulation of the L-cystine transporter, system xc-, in Müller cells. In this study, newly developed conditionally immortalized rat Müller cell lines (TR-MUL) from transgenic rats harboring the temperature-sensitive SV 40 large T-antigen gene were used as an in vitro model. TR-MUL cells express large T-antigen and grow well at 33°C with a doubling time of 30 h, but do not grow at 39°C. TR-MUL cells express typical Müller cell markers such as S-100, glutamine synthetase, and EAAT1/GLAST, whereas EAAT2/GLT-1 and EAAT5 are not detected. TR-MUL cells also exhibit little or no expression of glial fibrillary acidic protein. We found that TR-MUL5 cells exhibited [14C]L-cystine uptake activity and expressed xCT and 4F2hc, which involve system xc-. The uptake of [14C]L-cystine was significantly inhibited by L-glutamic acid and L-aspartic acid, whereas L-leucine had no effect. Following diethyl maleate (DEM) treatment, the glutathione concentration in TR-MUL5 cells was reduced in the first 24 h, then gradually recovered for more than 24 h. The L-cystine uptake rate and the xCT expression level in TR-MUL5 cells were enhanced by DEM treatment. In contrast, the 4F2hc expression level was unchanged. In conclusion, TR-MUL cells have the properties of Müller cells and exhibit system x c--mediated L-cystine uptake activity. The oxidative stress conditions following DEM treatment activate L-cystine transport in TR-MUL cells due to the enhanced transcription of the xCT gene.

Original languageEnglish
Pages (from-to)208-217
Number of pages10
Issue number3
Publication statusPublished - 2003 Sept 1
Externally publishedYes


  • Conditionally immortalized cell line
  • Diethyl maleate
  • Glutathione
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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