1998 Fiscal Year Final Research Report Summary
Prostaglandin D_2 inhibits expression of inducible nitric oxide mRNA and its therapeutic implication
| Project/Area Number |
09670703
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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 |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
UEHARA Yoshio Institution, Dept, Title Univ. of Tokyo. Health Service Center, Lecturer, 保健管理センター, 講師 (40184965)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Atsuo Institution, Dept, Title Univ. of Tokyo, Dept. of Med. , Associate Prof., 医学部, 助教授 (00150277)
NAGOSHI Hiroshi Institution, Dept, Title Univ. of Tokyo, Dept. of Med. , Staff, 医学部, 医員
SHIN Woo soo Institution, Dept, Title Univ. of Tokyo, Health Service Center, Staff, 保健管理センター, 助手 (10211971)
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| Project Period (FY) |
1997 – 1998
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| Keywords | prostaglandin D2 / cytokine / nitric oxide / nitric oxide synthase / intracellular receptor / interleukin / endotoxin shock / atherosclerosis |
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| Research Abstract |
We investigated the effects of prostaglandin D_2 (PGD_2) on nitric oxide formation by inducible NO synthase (iNOS) (Circulation Research 1998). Cytokine stimulated NO generation through iNOS induction in vascular smooth muscle cells (VSMC) in culture. PGD_2 significantly lessened this increase following cytokine stimulation. This reduction was accompanied by a decrease in iNOS mRNA, suggesting that PGD_2 inhibits transcription of iNOSmRNA and reduces biosynthesis of iNOS enzyme. The inhibitory effects were much greater in PGJ_2, a metabolite of PGD_2.
In addition. transfection of PGD synthase (PGDS) genes into VSMC increased PGD_2 biosynthesis and decreased iNOSmRNA and NO generation (submitted to Circulation Research). This indicates that the inhibitory effects of PGD_2 generation on NO formation are due to intracrine mechanism rather than receptor-mediated events. Delivery of PGDS would lead to treatment of vascular injury caused by excessive generation of NO.
In fact, administration of PGD_2 in advance attenuated the blood pressure reduction and lessened liver dysfunction in lipopolysaccharide-induced endotoxin shock. Vasorelaxation following acetylcholine was significantly attenuated in the rats given PGD_2 submitted to Life Science). This suggests that PGD_2 protects the cardiovascular system from events caused by excessive NO production.
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Research Products
(12 results)
