| Project/Area Number |
08671273
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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 |
Kidney internal medicine
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
OKUDA Toshihiro University of Tokyo, Health service center, Assistant professor., 保健管理センター, 助手 (80177170)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Yuichi University of Tokyo, 1st.Dept.Int.Med., Medical staff., 医学部・附属病院, 医員
OHARA Mamiko University of Tokyo, 1st.Dept.Int.Med., Assistant professor, 医学部・附属病院, 助手 (60261963)
UMEZU Michio University of Tokyo, 1st.Dept.Int.Med., Assistant professor., 医学部・附属病院, 助手 (70292935)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | mesangial cell / chloride / chloride blocker / protein kinase C / intracellulr Ca concentration / cell proliferation / thymidine / プロスタグランディン / c-AMP |
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| Research Abstract |
Cl^- is known to be an important regulator of mesanglal cell function including cell growth. Indeed, we reported decrease in ambient Cl^- concentration suppressed mesangial cell growth and this suggests the possibility that Cl^- channel blockers modify mesangial cell growth. Therefore, in the present study, we examined the effects of Cl^- channel blockers, anthracene-9-carboxylic acid and indanyloxyacetic acid-94(IAA-94), on[^3H]-thymidine incorporation in cultured rat mesangial cells. Both Cl^- channel blockers attenuated basal cell proliferation and IAA-94 suppressed platelet activating factor(PAF)or platelet derived growth factor(PDGF)-BB-stimulated cell growth. Further, IAA-94 suppressed PAF-or PDGF-BB-induced[Ca^<2+>]i responses. IAA-94 also attenuated[Ca^<2+>]i responses by these agents in the absence of extracellular Ca^<2+> and thapsigargin-induced[Ca^<2+>]i response was diminished by IAA-94 pretreatment. These observations indicate IAA-94 suppresses Ca^<2+> release from intracellular organellae. Prior activation of protein kinase C(PKC)by 12-o-tetradecanoylphorbol 13-acetate abolished the IAA-94-caused suppression of mesangial cell proliferation. In addition, IAA-94 suppressed PAF- or PDGF-BB-induced PKC translocation measured by [^3H]-phorbor-12,13-dibutyrate binding assay. IAA-94 also attenuated PKC activities in the presence of PAF and PDGF.These suggest PKC suppression is involved in cell growth inhibition by IAA-94. We concluded that Cl^- channel blocker attenuates mesangial cell proliferation. This cell growth suppression might be though its effect on Ca^<2+> signaling and PKC pathway.
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