| Project/Area Number |
16209023
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Gunma University |
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Principal Investigator |
KOMINATO Yoshihiko (2006) Gunma University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30205512)
岸 紘一郎 (2004-2005) 群馬大学, 大学院・医学系研究科, 教授 (30169841)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Tamiko Gunma University, Gradual School of Medicine, Assistant, 大学院・医学系研究科, 助手 (40008561)
小湊 慶彦 群馬大学, 大学院・医学系研究科, 助教授 (30205512)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥44,460,000 (Direct Cost: ¥34,200,000、Indirect Cost: ¥10,260,000)
Fiscal Year 2006: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2005: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2004: ¥31,330,000 (Direct Cost: ¥24,100,000、Indirect Cost: ¥7,230,000)
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| Keywords | Deoxyribonuclease I / QGP-1 cell / Hypoxia / Transcription / Myocardial infarction / Promoter / 膵臓癌細胞GSP1 |
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| Research Abstract |
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
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