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Molecular biology of vasoactive substances

血管活性物质的分子生物学

基本信息

批准号：
06044129
负责人：
NAKAO Kazuwa
金额：
$ 2.82万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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.

用培养的新生大鼠心室肌细胞建立心肌肥厚模型，脑钠肽（BNP）mRNA在1小时内升高并达到最高水平，而转录抑制剂可完全抑制BNP mRNA的表达。克隆的人BNP基因5 '侧翼区的启动子活性在富含CT的序列（-1288 ~-1095）缺失后降低到30%。BNP基因定位于人类1号染色体。用RT-PCR方法检测到两个新的人内皮素A受体（ET-AR）基因转录本，分别缺失199 bp和327 bp，缺失序列分别对应于外显子4和外显子3、4，表明这两个ET-AR基因转录本是RNA选择性剪接的产物。该负调控区位于小鼠血管紧张素Ⅱ 2型（AT_2）受体基因的-453 ~-225之间，其中存在干扰素调节因子（IRF）结合基序。IRF-2减弱了生长和融合的R3 T3细胞中的AT 2受体表达，而IRF-1仅增强了融合细胞中的AT 2受体表达。人前列环素受体基因跨越约7.0 kb，由三个外显子组成，被分配到19号染色体。转录起始位点定位在ATG起始密码子上游870-872 bp处。1.2kb的5 '侧翼区缺乏传统的TATA和CCAAT盒，但它含有几个顺式作用调控元件，包括一个反向的CCAAT盒和两个拷贝的SP-1结合位点。