1991 Fiscal Year Final Research Report Summary
RADICAL SCAVENGER ACTIVITY OF A NOVEL ENZYMATICALLY SYNTHESIZED PROVITAMINC AND ITS APPLICATION TO AUTOIMMUNE DISEASE
| Project/Area Number |
02670996
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
YAMAMOTO Itaru FACULTY OF PHARMACEUTICAL SCIENCES,OKAYAMA UNIVERSITY PROFESSOR, 薬学部, 教授 (20028848)
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| Project Period (FY) |
1990 – 1991
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| Keywords | stable ascorbate deribative / alpha-glucosidase / immunopotentiation / autoimmune disease / radical scavenging activity / AA-2G / 抗白内障作用 |
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| Research Abstract |
We have synthesized a novel stable ascorbate derivative, 2-0-alpha-glucopyranosyl-L-ascorbic acid (AA-2G) by enzymatic glucosylation with mammalian alpha-glucosidase, rice seed alpha-glucosidase and CGTase from Baccilus stearothermophylus. This vitamin derivative exhibits vitamin C activity in vitro and in vivo such as the promotion of collagen synthesis and anti-scurvic activty after cleavage by cellular alpha-glucosidase.
In this study I examined wheather AA-2G exhibits stimulatory activity of antibody production and radical scavenging actiivity, to evaluate the possibility of this vitamin for application to the radical oxigen-associated diseases such as cancer and autoimmune diseases.
As a result, AA-2G strongly stimulated the anti-SRBC PFC response in cultured splenocytes at doses of 0.1-5mM concentrations, whereas ascorbic acid (AsA) was without effect. However, repeated additions (total ten times) of AsA during the experimental periods exhibited the stimulatory effect which is equi
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valent to a single dose of AA-2G.In additon, the stimulatory response by AA-2G was completely blocked in the presence of alpha-glucosidase inhibitor, castanospermin. These results suggest that the immunopotentiating activity of AA-2G is due to ascorbic acid cleaved by cellular alpha-glucosidase.
AsA at high concentrations showed the cytotoxicity upon the cultured lymphocytes or fibroblastes, which was restored by the addition of catalase, while AA-2G did not. Cellular level of ascorbate after exposure to ascorbic acid was much higher than that of AA-2G, indicating that AA-2G slowly release AsA after digestion by alpha-glucosidase through the experiment periods.
Radical scavenging activity of AA-2G was evaluated in neutral pH buffer solution. As a result, AA-2G itself was unexpectedly observed to have radical acavenging actvity, although its activity was weeker than that of AsA.
Taken together, a novel stable ascorbate derivative, AA-2G could be expected to be used for treatments of autoimmune diseases which are assumed to be caused by oxidateve stress. Less
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