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

我们证明，血清DNase I活性可作为急性心肌梗死（AMI）早期检测的新诊断标志物; AMI患者症状发作后3小时内血清DNase I活性水平突然升高，允许在准确的CK-MB和c-TnT结果可用之前诊断AMI。此外，我们研究了经皮冠状动脉介入治疗（PCI）过程中引起短暂缺血后血清DNA酶I水平的变化。血清DNase I活性在PCI手术完成后3 h显著升高。然而，AMI或PCI期间缺血诱导的血清DNase I活性升高的机制仍有待阐明。为了阐明这一现象的分子基础，重要的是要了解人类DNA酶I基因（DNASE 1）表达的调控机制。我们首先定位了人胰腺和产生人胰腺DNA酶I的DNA酶1的转录起始位点， ...更多信息 结果表明，在QGP-1基因外显子1上游12 kb处发现了一个新的转录起始位点。这个起始位点标志着一个替代起始外显子，命名为1a。在胰腺和QGP-1细胞中，外显子1和1a同时用作转录起始外显子。启动子分析EMSA和染色质免疫沉淀分析与QGP-1细胞系表明，启动子区的外显子1a中的Sp1转录因子是特异性参与启动子活性。这是第一个被鉴定为负责脊椎动物DNA酶I基因表达的转录因子。此外，RT-PCR分析表明，在胰腺和QGP-1细胞中的人DNA酶1前体mRNA的选择性剪接。在所鉴定的八种选择性剪接产物中，只有两种转录本可以翻译成完整的DNA酶I蛋白。这些结果表明，人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

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