Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants|
|Research Institution||University of Fukui(2004-2006)|
YASUDA Toshihiko University of Fukui, Faculty of Medical Sciences, Professor, 医学部, 教授 (80175645)
IIDA Reiko University of Fukui, Faculty of Medical Sciences, Assistant, 医学部, 助手 (40139788)
KAWAI Yasuyuki Kanazawa Medical University, Assistant, 医学部, 助手 (40324157)
UEKI Misuzu University of Fukui, Faculty of Medical Sciences, Instruction Official, 医学部, 教務職員 (00165656)
KOMINATO Yoshihiko Gunma University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (30205512)
岸 紘一郎 群馬大学, 医学部, 教授 (30169841)
|Project Period (FY)
2003 – 2006
Completed(Fiscal Year 2006)
|Budget Amount *help
¥43,680,000 (Direct Cost : ¥33,600,000、Indirect Cost : ¥10,080,000)
Fiscal Year 2006 : ¥5,200,000 (Direct Cost : ¥4,000,000、Indirect Cost : ¥1,200,000)
Fiscal Year 2005 : ¥6,760,000 (Direct Cost : ¥5,200,000、Indirect Cost : ¥1,560,000)
Fiscal Year 2004 : ¥14,430,000 (Direct Cost : ¥11,100,000、Indirect Cost : ¥3,330,000)
Fiscal Year 2003 : ¥17,290,000 (Direct Cost : ¥13,300,000、Indirect Cost : ¥3,990,000)
|Keywords||Forensic Science / Age-estimation / Genomics / Proteomics / Age-related alterations / Gene expression / Biomarkers / Deoxyribonuclease I / フィブロネクチン / 年齢依存性生体分子 / 一次構造 / ペルオキシソーム / 法医学的応用 / 虚血 / 血清 / 心筋梗塞 / ミトコンドリアDNA / deoxyribonuclease / ペルオキシゾーム / 活性酸素|
1. It was clarified that the application of two non isotopic techniques as a genomics approach-fluorescence differential display-PCR to the first screening and the comparative RT-PCR to the subsequent confirmation-has allowed us to identify and characterize novel genes expressed in an age-related manner.
2. Using the method describe above, we succeeded in identification of an age-dependently expressed gene encoding a novel protein, Mpv17-like protein, M-LP in mouse kidney, then characterized its molecular-biological aspects such as the structure of cDNA and gene, and identification of spliced isoforms. Cell-biological analysis demonstrated that M-LP localized in peroxisomal membrane: we elucidated the peroxisomal membrane targeting signal and membrane topology of M-LP. Furthermore, M-LP may be involved in metabolism of reactive oxygen species through regulating expression of antioxidant enzyme genes.
3. We identified and characterized a human homolog of the M-LP as a marker fiage-estimat
4. We succeeded in determination of the complete primary structure of a young age-specifi urinary glycoprotein, Ugl-Y, which had previously been identified by a proteomics approach Ugl-Y was clarified to be derived from a. young age-specific proteolysis of one of the matri proteins, fibronection.
5. Characterization of age-related alterations in the mitochondrial DNA (mtDNA) of various tissues revealed that mtDNA, its transcripts and mtDNA encoded products generally increase in content during the course of aging.
6. We have previously found levels of deoxyribonuclease I (DNase I) activity in human pituitary gland to alter in an age-related manner. An abrupt elevation of serum DNase I activity was observed within approximately 3 hours of the onset of acute myocardial infarction (AMI. Therefore, serum DNase I could be used as a new diagnostic marker for the early detection of AMI.
7. Transient myocardial ischemia during percutaneous coronary intervention induced a significant elevation of serum DNase I activity. Increased activity of the enzyme may prove useful as a sensitive marker for detection of transient myocardial ischemia.
8. Possible regulation of human DNase I gene expression, in which transcription factor Spl is involved, was elucidated. Less