| Project/Area Number |
06044129
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKAO Kazuwa Kyoto University, Graduate School of Medicine, professor, 医学研究科, 教授 (00172263)
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| Co-Investigator(Kenkyū-buntansha) |
SUGA Shin-ichi (SAITOH Yoshihiko) Kyoto University, Graduate School of Medicine, Assistant, 医学研究科, 助手 (30250260)
ITOH Hiroshi Kyoto University, Graduate School of Medicine, Assistant, 医学研究科, 助手 (40252457)
YOSHIMASA Takaaki Kyoto University, Graduate School of Medicine, Assistant, 医学研究科, 助手 (00252429)
TANAKA Issei Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (80179738)
YANAGIZAWA Masashi University of Texas, South Western Medical Center, Associate Professor, Associate
INAGAMI Tadashi Vanderbilt University, School of Medicine, professor, Professor
DZAU Victor j. Stanford University, School of Medicine, professor, Professor
YANAGISAWA M Howard Hughes Medical, Institute・Univ. of, Associate
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1995: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | BNP / endothelin-A receptor / AT_2 receptor / Prostacyclin receptor / ナトリウム利尿ペプチド / アンジオテンシンII受容体 / エンドセリン / エンドセリン受容体 / 遺伝子 / トランスジェニックマウス / ジーンターゲッティング / 遺伝子導入 |
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| Research Abstract |
Brain natriuretic peptide (BNP) mRNA increased and reached a maximal level within 1 h in a model of cardiac hypertrophy using cultured neonatal ratventricular cardiocytes, which was completely diminished by a transcriptional inhibitor. The promotor activity of the cloned 5'-flanking region of human BNP gene was reduced to 30% when the CT-rich sequences (-1288 to -1095) were deleted. The BNP gene was assigned to human chromosome 1. Two novel transcripts of the human endothelin-A receptor (ET-AR) gene contained deletions of 199 bp and 327 bp were demonstrated using RT-PCR.The deleted sequences corresponded to exon 4 and exons 3 and 4, respectively, indicating these ET-AR transcripts result from alternative RNA splicing. The putative negative regulatory region was located between -453 and -225 of mouse angiotensin II type 2 (AT_2) receptor gene, in which the interferon regulatory factor (IRF) binding motif was identified. IRF-2 attenuated the AT2 receptor expression in both growing and confluent R3T3 cells, whereas IRF-1 enhanced AT2 receptor expression in the confluent cells only. The human prostacyclin receptor gene spanned approximately 7.0 kb and was composed of three exons, which was assigned to chromosome 19. The transcription initiation sites were mapped 870-872 bp upstream to the ATG start codon. The 1.2-kb 5'-flanking region lacked conventional TATA and CCAAT boxes, but it contained several cis-acting regulatory elements including an inverted CCAAT box and two copies of SP-1 binding sites.
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