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Serum DNase I activity can be used as a sensitive marker for detection of acute myocardial infarction

血清DNase I活性可作为检测急性心肌梗死的敏感标志物

基本信息

批准号：
16209023
负责人：
KOMINATO Yoshihiko
金额：
$ 28.45万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16209023/
关键词：
Deoxyribonuclease I QGP-1 cell Hypoxia Transcription Myocardial infarction Promoter 膵臓癌細胞GSP1

项目摘要

We demonstrated that serum DNase I activity could be used as novel diagnostic marker for the early detection of acute myocardial infarction (AMI) ; abrupt elevation of serum DNase I activity levels occurs within 3h of the onset of symptoms in patients with AMI, permitting the diagnosis of AMI before accurate CK-MB and c-TnT results become available. Moreover, we investigated alterations in serum DNase I levels after transient ischemia induced during percutaneous coronary intervention(PCI). Serum DNase I activity had risen significantly from base line by 3h after completion of the PCI procedure. However, the mechanism for the elevation of serum DNase I activity induced by ischemia during AMI or PCI remain to be elucidated. To elucidate the molecular basis of this phenomenon, it is important to understand the regulatory mechanism of the human DNase I gene(DNASE1) expression. We first mapped the transcription start sites of DNASE1 in human pancreas and in the DNase I producing human pancr … More eatic cancer cell line QGP-1, and revealed a novel site 12kb upstream of exon 1, which was previously believed to be the single transcription starting exon. This initiation site markes an alternative starting exon, designated 1a. Exon 1 and 1a were used simultaneously as transcription starting exon in pancreas and QGP-1 cells. Promoter assay EMSA and chromatin immunoprecipitation analysis with QGP-1 cell lines showed that the promoter region of exon 1a in which the Sp1 transcription factor is specifically involved in promoter activity. This is the first to be identified as a transcription factor responsible for gene expression of vertebrate DNase I gene. Furthermore, RT-PCR analysis indicated alternative splicing of human DNase 1 pre-mRNA in pancreas and QGP-1 cells. Only two transcripts among eight alternative splicing products identified can be translated to produce intact DNase I protein. These results suggested that human DNase 1 expression is regulated through the use of alternative promoter and alternative splicing. Less

结果表明，血清dna酶I活性可作为早期检测急性心肌梗死（AMI）的新诊断指标；AMI患者出现症状后3小时内血清DNase I活性水平突然升高，可在获得准确的CK-MB和c-TnT结果之前诊断AMI。此外，我们研究了经皮冠状动脉介入治疗（PCI）期间短暂缺血后血清dna酶I水平的变化。完成PCI手术后3h，血清DNase I活性从基线显著升高。然而，AMI或PCI期间缺血引起血清dna酶I活性升高的机制尚不清楚。为了阐明这一现象的分子基础，了解人类dna酶1基因（DNASE1）表达的调控机制是很重要的。我们首先在人类胰腺和产生胰腺癌的dna酶I细胞系QGP-1中绘制了DNASE1的转录起始位点，并在1号外显子上游12kb处发现了一个新的位点，该位点以前被认为是单转录起始外显子。这个起始位点标记了另一个起始外显子，命名为1a。在胰腺和QGP-1细胞中同时使用外显子1和1a作为转录起始外显子。QGP-1细胞系的启动子分析（EMSA）和染色质免疫沉淀分析表明，Sp1转录因子特异性参与启动子活性的1a外显子启动子区域。这是第一个被确定为负责脊椎动物dna酶I基因表达的转录因子。此外，RT-PCR分析显示胰腺和QGP-1细胞中存在不同的人DNase 1前mrna剪接。在鉴定的8个备选剪接产物中，只有2个转录本可以翻译成完整的dna酶I蛋白。这些结果表明，人类DNase 1的表达是通过使用选择性启动子和选择性剪接来调节的。少