Essential role of poly(ADP-ribosyl)ation in maintenance of spermatogonial stem cells

• Project/Area Number: 23590097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka Ohtani University
• Principal Investigator: TAKEHASHI MASANORI 大阪大谷大学, 薬学部, 准教授 (10378862)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 精子幹細胞 / ポリ(ADP-リボース) / 多能性幹細胞 / 発生・分化 / 再生医療 / ポリ(ADP-リボース） / ポリ(ＡＤＰ-リボース)

Research Abstract

Spermatogonial stem cells (SSCs) can proliferate in vitro in the presence of glial cell line-derived neurotrophic factor, a self-renewal factor for SSCs. These cultured SSCs are called germline stem (GS) cells. In previous study, we examined the effect of PARP inhibitor, inhibition of poly(ADP-ribosyl)ation, on GS cells. Inhibition of poly(ADP-ribosyl)ation suppressed cell proliferation of GS cells, and induced cell death. In order to identify the causative genes that is involved in the pathway leading to the suppression of cell proliferation, the gene expression and protein phosphorylation analyses were carried out. Some genes in p53 signaling pathway were up-regulated after addition of PARP inhibitors. We then investigated activation of p53 by detection of its phosphorylation site. The phosphorylation was increased after addition of PARP inhibitors. These results suggest that poly(ADP-ribosyl)ation regulates activity of p53 and thus p53 signaling pathway in GS cells.

Research Products

• [Journal Article] Hybridization of testis-derived stem cells with somatic cells and embryonic stem cells in mice (2012)
  • Author(s): Takehashi M, Tada M, Kanatsu-Shinohara M, Morimoto H, Kazuki Y, Oshimura M, Tada T, Shinohara T
  • Journal Title: Biol Reprod Volume: 86
  • Peer Reviewed
• [Journal Article] Hybridization of testis-derived stem cells with somatic cells and embryonic stem cells in Mice (2012)
  • Author(s): Takehashi, M., Tada, M., Kanatsu-Shinohara, M., Morimoto, H., Kazuki, Y., Oshimura, M., Tada, T. and Shinohara, T
  • Journal Title: Biol. Reprod Volume: 86(6) Issue: 6 Pages: 178-178
  • DOI: 10.1095/biolreprod.112.098988
  • Peer Reviewed
• [Journal Article] Mammalian selenocysteine lyase is involved in selenoprotein biosynthesis (2011)
  • Author(s): Kurokawa S, Takehashi M, Tanaka H, Mihara H, Kurihara T, Tanaka S, Hill K, Burk R, Esaki N
  • Journal Title: J Nutr Sci Vitaminol (Tokyo) Volume: 57 Pages: 298-305
  • NAID: 130001373002
  • Peer Reviewed
• [Journal Article] Inhibition of poly(ADP-ribose) polymerase-1 attenuates the toxicity of carbon tetrachloride (2011)
  • Author(s): Banasik M, Stedeford T, Strosznajder RP, Takehashi M, Tanaka S, Ueda K
  • Journal Title: J Enzyme Inhib Med Chem Volume: 26 Pages: 883-889
  • Peer Reviewed
• [Journal Article] Inhibition of poly(ADP-ribose) polymerase-1 attenuates the toxicity of carbon tetrachloride. (2011)
  • Author(s): Banasik M, et al.
  • Journal Title: J Enzyme Inhib Med Chem Volume: 26 Pages: 883-889
  • Peer Reviewed
• [Journal Article] Mammalian selenocysteine lyase is involved in selenoprotein biosynthesis. (2011)
  • Author(s): Kurokawa S, et al.
  • Journal Title: J Nutr Sci Vitaminol (Tokyo) Volume: 57 Pages: 298-305
  • Peer Reviewed
• [Presentation] PARP-1による神経幹細胞の増殖制御 (2014)
  • Author(s): 奥田明子, 他
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-28
• [Presentation] 多能性幹細胞の初期化能の解析 (2014)
  • Author(s): 中嶋瀬里奈, 他
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-28
• [Presentation] ポリ(ADP-リボシル)化の制御が精子幹細胞に与える影響 (2014)
  • Author(s): 小野友久, 他
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-28
• [Presentation] PARP-1による神経幹細胞の増殖制御 (2014)
  • Author(s): 奥田明子，竹橋正則，田中静吾
  • Organizer: 薬学会134年会
  • Place of Presentation: 熊本
• [Presentation] 多能性精子幹細胞の初期化能の解析 (2014)
  • Author(s): 中嶋瀬里奈，片山健太郎，奥田明子，田中静吾，竹橋正則
  • Organizer: 薬学会134年会
  • Place of Presentation: 熊本
• [Presentation] ポリ(ADP-リボシル)化の抑制が精子幹細胞に与える影響 (2014)
  • Author(s): 小野友久，中嶋瀬里奈，奥田明子，田中静吾，竹橋正則
  • Organizer: 薬学会134年会
  • Place of Presentation: 熊本
• [Presentation] PARP-1阻害剤のよるp21を介した細胞周期制御 (2013)
  • Author(s): 奥田明子, 他
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] PARP-1阻害剤が神経幹細胞の細胞周期に与える影響について (2012)
  • Author(s): 前田藍佳, 他
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-29
• [Presentation] PARP-1阻害剤によるp21を介した細胞周期制御
  • Author(s): 奥田明子
  • Organizer: 日本薬学会第１３３年会
  • Place of Presentation: 横浜