2004 Fiscal Year Final Research Report Summary
Study of the cleavage of diphtheria taxin receptor by ADAM12
| Project/Area Number |
15590407
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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 |
Bacteriology (including Mycology)
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
UMATA Toshiyuki University of Occupational and Environmental Health, Japan Research Facility for Occupational and Environmental Health, Associate Professor, 産業医学研究支援施設, 助教授 (30213482)
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| Co-Investigator(Kenkyū-buntansha) |
OHTSUBO Motoaki Hiroshima University, Rrsearch institute for Radiation Biology and Medicine, Research Associate, 原爆放射線医学研究所, 助手 (10211799)
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| Project Period (FY) |
2003 – 2004
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| Keywords | diphtheria toxin receptor / lysophosphatidic acid / cleavage of extracelular domain / ADAM |
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| Research Abstract |
Lysophosphatidic acid (LPA) induces ectodomain shedding of diphtheria toxin receptor (DTR) in Vero cells. It has also been known that LPA generates reactive oxygen species (ROS). In the present study, to clarify whether ROS were implicated in LPA-induced DTR shedding, we investigated the effects of N-acetyl-L-cysteine (NAC), a ROS scavenger. NAC inhibited LPA-induced DTR shedding, but another ROS scavengers (ascorbic acid and a-tocopherol) did not. However, NAC, ascorbic acid and a-tocopherol suppressed ROS production in LPA-treated cells. Thus, NAC inhibited shedding in ROS independent manner. NAC only had a sulfhydryl group in three reagents, so, another reagents (L-cysteine, cysteamine) having sulfhydryl group were examined. These reagents also inhibited shedding. However, NAC treated with oxidizing agent did not inhibit shedding. These results suggest that the sulfhydryl group in NAC is important for shedding inhibition. ADAM has a cysteine-zinc bond that exists between the critical cysteine of the prodomain and the zinc atom of the active site. So, we examined whether NAC influenced to ADAM family. NAC also inhibited HB-EGF shedding induced by 4-aminophenylmercuric acetate (APMA) which activates latent metalloproteases by inducing autocatalytic cleavage and removal of the enzyme prodomain inhibitory region. Altogether, these results suggest that inhibitory effect of NAC on LPA-induced shedding might be related to inhibition of ADAM protease.
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Research Products
(13 results)
