2005 Fiscal Year Final Research Report Summary
Nuclear translocation of antioxidant enzymes and ROS metabolism
| Project/Area Number |
15590258
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
SUZUKI Keiichirou Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (70221322)
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| Co-Investigator(Kenkyū-buntansha) |
OOKAWARA Tomomi Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50330452)
FUJIWARA Noriko Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (10368532)
EGUCHI Hironobu Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (60351798)
KUROTSU Tositsugu Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20098528)
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| Project Period (FY) |
2003 – 2005
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| Keywords | ROS / superoxside dismutase / EC-SOD / oxidative stress / arteriosclerosis / HB-EGF |
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| Research Abstract |
Extracellular superoxide dismutase (EC-SOD) is the only known secretory SOD isoenzyme. EC-SOD has a positively-charged heparin-binding domain at the C-terminus and it has been thought that this domain and the secretory nature could allow the enzyme characteristic multiple distributions after the secretion.
1.We have purified recombinant EC-SOD protein from the cultured medium of the stably mouse EC-SOD expressing cell line, CHO-EK.
2.Physical training apparently decreased EC-SOD level in humam plasma as a reflection of the increased binding capacity in tissues to EC-SOD and heavy physical examination, which was simulated the ischemic-reperfusion injuries, brought a release of tissue bound EC-SOD to the blood stream.
3.3T3-L1 cells incorporated EC-SOD from the medium and a significant fraction of the material taken up was localized in the nucleus. Oxidative stress on the 3T3-L1 cell downregulated the uptake of EC-SOD and the nuclear translocation of the incorporated EC-SOD was clearly enhanced by H_2O_2 treatment.
4.EC-SOD purified from the human lung tissue was fractionated through heparin affinity chromatography and clarified the relation between the modification at C-terminus and heparin affinity.
5.Investigation using RASMC and the recombinant EC-SOD revealed that RASMC incorporated EC-SOD from the medium and heparin interfered the binding of EC-SOD to RASMC. Moreover, TPA and hydrogen peroxide induced the production of ROS in RASMC and gene expression of HB-EGF and pre-treatment of the RASMC with EC-SOD suppressed the induction of HB-EGF induction, suggesting that EC-SOD inhibited the EGF signaling evoked by ROS stimulation in RASMC.
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Research Products
(18 results)
