Study of the mechanism of cardiac hypertrophy induction by calcium signal and an attept to establish a procedure to regulate cardiac hypertrophy

• Project/Area Number: 15590776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: TSURUMI UNIVERSITY
• Principal Investigator: MIYATAKE Yoshiko Tsurumi University, Dept.dentistry, lecturer, 歯学部, 講師 (10267213)
• Co-Investigator(Kenkyū-buntansha): NEJIMA Jyun Tsurumi University, Dept.dentistry, Professor, 歯学部, 教授 (00164658) ; MIYATAKE Shoichiro Tokyo Metropolitan Organization For medical Research Tokyo Metropolitan Institute of Medical Science, Dept Immunology, Laboratory head, 東京都臨床医学総合研究, 副参事研究員 (30239420)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
• Keywords: NFAT / calcineurin / transcription factor / alpherscreen / cardiachypertrophy / 心筋細胞 / カリシニューリン / 分子間相互作用

Research Abstract

We tried to develop specific chemical compounds that block transcription factor NFAT family and its regulatory factor calcineurin involved in cardiac hypertrophy. An experimental system to analyze the interaction of NFAT and calcineurin rapidly and quantitatively by alpher screenj method was developed. By utilizing this system, screening of peptides and chemical compounds that interfere NFAT-calcineurin interaction was performed. Several compounds showed interfering activity. Some of those compounds inhibited NFAT dependent transcription activity detected by reporter assay. Furthermore some of those compounds suppressed the expression induction of cytokine genes upon stimulation in lymphocytes.
Comparison of the calcineurin binding region 1(CNBR1) located near the N terminus and the CNBR2 located at the C terminal end of the calcium regulatory domain of each NFAT subtype was carried out. and subtype specificity was not observed. The region between CNBR1 and CNBR2 that contains NLS(nuclear localization sequence) showed the calcineurin binding activity. The peptides derived from this region showed the inhibitory activity on the binding of NFAT1 and NFAT2 but not that of NFAT3 and NFAT4 indicating the subtype specificity.

Research Products

• [Journal Article] GATA-3 suppresses IFN-γ promoter activity independently of binding to cis-regulatory elements. (2004)
  • Author(s): Kaminuma, O., Kitamura, F., Kitamura, N., Miyagishi, M., Taira, K., Yamamoto, K., Miura, O., Miyatake, S.
  • Journal Title: FEBS Lett. 570 Pages: 53-58
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] GATA-3 suppresses IFN-γ promoter activity independently of binding to cis-regulatory elements. (2004)
  • Author(s): Kaminuma, O., Kitamura, F., Kitamura, N., Miyagishi, M., Taira, K., Yamamoto, K., Miura, O., Miyatake, S
  • Journal Title: FEBS lett. 570 Pages: 53-58
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] GATA-3 suppresses IFN-γ promoter activity independently of binding to cis-regulatory elements. (2004)
  • Author(s): Kaminuma, O., Kitamura, F., Kitamura, N., Miyagishi, M., Taira K., Yamamoto, K., Miura, O., Miyatake, S.
  • Journal Title: FEBS Letter 570 Pages: 53-58