| Project/Area Number |
11694249
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokyo (Graduate School of Pharmaceutical Sciences) |
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Principal Investigator |
KATADA Toshiaki The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept.of Physiol.Chem., Professor, 大学院・薬学系研究科, 教授 (10088859)
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| Co-Investigator(Kenkyū-buntansha) |
KONTANI Kenji The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept.of Physiol.Chem., Research fellow, 大学院・薬学系研究科, 助手 (30302615)
HOSHINO Shin-ichi The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept.of Physiol.Chem., Research fellow, 大学院・薬学系研究科, 助手 (40219168)
NISHINA Hiroshi The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept.of Physiol.Chem., Associate Professor, 大学院・薬学系研究科, 助教授 (60212122)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | lymphocytes / CD38 / ecto-enzyme / NADase / retinoic acid / PC-1 / phosphodiesterase |
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| Research Abstract |
Ecto-form NADase activity induced by retinoic acid (RA) in human HL-60 cells is due to CD38, which has an amino acid sequence homologous to Aplysia ADP-ribosyl cyclase. CD38 catalyzes not only the hydrolysis of NAD^+, but also the formation and hydrolysis of cyclic ADP-ribose (cADPR), that is a novel mediator or modulator of Ca^<2+> release from intracellular Ca^<2+> stores. In the present study, we investigated the functions and properties of CD38 and its related ecto-enzyme, PC-1. 1. CD38 was capable of hydrolyzing the N-glycoside bond of many compounds other than NAD^+. 2. CD38 was abundantly present in rat astrocytes in addition to lymphocytes, and the cell-surface CD38 was rapidly inactivated upon incubation with the enzyme substrates. 3. Soluble and membrane-bound forms of PC-1, which had been induced in human Jurkat T cells upon culture with a cAMP analog, were identified and characterized enzymatically and structurally. 4. Both PC-1 molecules possessed phosphodiesterase/pyrophosphatase activity, and the enzymic activity of soluble PC-1 could be utilized to search for its interacting molecules. 5. Glycosaminoglycans, such as heparin and heparan sulfate in extracellular matrix, were capable of binding to PC-1 and inhibited its phosphodiesterase activity in a manner competing with the enzyme substrates. 6. A homologue of human PC-1 was also present in C.elegans, and it possessed phosphodiesterase/pyrophosphatase activity. The enzymic activity was localized in the cell surface. Thus, PC-1 may function as an adhesion molecule to associate with glycosaminoglycans in extracellular matrix.
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