Selenoprotein S Suppression Enhances the Late Stage Differentiation of Proerythrocytes Via SIRT1

  • Yang, Hee-Young (Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University) ;
  • Chung, Kyoung-Jin (Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University) ;
  • Park, Hyang-Rim (Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University) ;
  • Han, Seong-Jeong (Department of Biochemistry, Center for Aging and Geriatrics, Chonnam National University Medical School) ;
  • Lee, Seung-Rock (Department of Biochemistry, Center for Aging and Geriatrics, Chonnam National University Medical School) ;
  • Chay, Kee-Oh (Department of Biochemistry, Center for Aging and Geriatrics, Chonnam National University Medical School) ;
  • Kim, Ick-Young (Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University) ;
  • Park, Byung-Ju (Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University) ;
  • Lee, Tae-Hoon (Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University)
  • 투고 : 2010.03.24
  • 심사 : 2010.06.18
  • 발행 : 2010.06.30

초록

Selenoprotein S (SelS) is widely expressed in diverse tissues where it localizes in the plasma membrane and endoplasmic reticulum. We studied the potential function of SelS in erythrocyte differentiation using K562 cells stably over-expressing SelS wild-type (WT) or one of two SelS point mutants, $U_{188}S$ or $U_{188}C$. We found that in the K562 cells treated with $1\;{\mu}M$ Ara-C, SelS gradually declined over five days of treatment. On day 4, intracellular ROS levels were higher in cells expressing SelS-WT than in those expressing a SelS mutant. Moreover, the cell cycle patterns in cells expressing SelS-WT or $U_{188}C$ were similar to the controls. The expression and activation of SIRT1 were also reduced during K562 differentiation. Cells expressing SelS-WT showed elevated SIRT1 expression and activation (phosphorylation), as well as higher levels of FoxO3a expression. SIRT1 activation was diminished slightly in cells expressing SelS-WT after treatment with the ROS scavenger NAC (12 mM), but not in those expressing a SelS mutant. After four days of Ara-C treatment, SelS-WT-expressing cells showed elevated transcription of $\beta$-globin, $\gamma$-globin, $\varepsilon$-globin, GATA-1 and zfpm-1, whereas cells expressing a SelS mutant did not. These results suggest that the suppression of SelS acts as a trigger for proerythrocyte differentiation via the ROS-mediated downregulation of SIRT1.

키워드

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