Uptake mechanisms study and molecular analysis of biomedicine in tissue culture system.

• Project/Area Number: 24590218
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: SUZUKI Toshihiro 明治薬科大学, 薬学部, 講師 (80322527)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 酵素補充療法 / マンノース６リン酸レセプター / バイオ医薬品 / 薬物動態 / 血管内皮細胞

Outline of Final Research Achievements

To estimate uptake mechanism of biomedicine such as alpha-galactosidase (GLA), we developed the evaluation system of uptake analysis system using in vitro primary culture cell. We proved GLA uptake dependent mannose-6-phosphate receptor (M6PR) in primary cultured cell. However, M6PR independent uptake was obtained in renal proximal tubule epithelial cells and renal cortical epithelial cells. These results correlate with in vivo pharmacokinetics. These results suggest that our cell culture system is useful for pharmacokinetic study in pre-clinical.

Research Products

• [Journal Article] Potential anti-angiogenesis effects of p-terphenyl compounds from Polyozellus multiplex (2014)
  • Author(s): Nagasawa I, Kaneko A, Suzuki T, Nishio K, Kinoshita K, Shiro M, Koyama K.
  • Journal Title: J. Nat. Prod. Volume: 77 Issue: 4 Pages: 963-968
  • DOI: 10.1021/np401046z
  • Peer Reviewed / Open Access
• [Journal Article] Development of a highly sensitive immuno-PCR assay for the measurement of alpha-galactosidase A protein levels in serum and plasma (2013)
  • Author(s): Nakano, S. Morizane, Y. Makisaka, N. Suzuki, T. Togawa, T. Tsukimura, T. Kawashima, I. Sakuraba, H. Shibasaki, F.
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e78588-e78588
  • DOI: 10.1371/journal.pone.0078588
  • Peer Reviewed
• [Journal Article] Impaired neural differentiation of induced pluripotent stem cells generated from a mouse model of Sandhoff disease. (2013)
  • Author(s): Ogawa Y, Tanaka M, Tanabe M, Suzuki T, Togawa T, Fukushige T, Kanekura T, Sakuraba H, Oishi K.
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e55856-e55856
  • DOI: 10.1371/journal.pone.0055856
  • Peer Reviewed
• [Journal Article] Database of the clinical phenotypes, genotypes, and mutant arylsulfatase B structures in mucopolysaccharidosis type VI (2012)
  • Author(s): Saito S, et al
  • Journal Title: J.Hum.Genet. Volume: 57 Issue: 4 Pages: 280-282
  • DOI: 10.1038/jhg.2012.6
  • Peer Reviewed
• [Journal Article] Efficient uptake of recombinant α-galactosidase A produced with a gene-manipulated yeast by Fabry mice kidneys (2011)
  • Author(s): Tsukimura, et al
  • Journal Title: Mol.Med. Volume: 18 Issue: 1 Pages: 76-82
  • DOI: 10.2119/molmed.2011.00248
  • Peer Reviewed
• [Presentation] Contribution of miR-205 in gefitinib-resistant lung cancer cell lines (2014)
  • Author(s): Suzuki T, Nagasawa I, Yamaoka T, Ohmori T, Nishio K, Koyama K, Ogasawara Y
  • Organizer: Annual Meeting of American Association for Cancer Research
  • Place of Presentation: San Diego CA, USA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] ヒト正常組織由来細胞を用いたα-ガラクトシダーゼ取り込み機構の検討 (2014)
  • Author(s): 鈴木 俊宏、石原茉祐花 、小林敦子 、月村 考宏、兎川 忠靖、櫻庭 均、小笠原裕樹
  • Organizer: 日本薬学会134年会
  • Place of Presentation: 熊本
• [Presentation] ヒト正常組織由来培養細胞における組換えリソソーム酵素の取り込み (2012)
  • Author(s): 鈴木俊宏、兎川忠靖、月村考宏、櫻庭 均
  • Organizer: 日本生化学会大会
  • Place of Presentation: 福岡