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Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage.

Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage. Research Abstract Details 

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  • Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage. Abstract Text:

    atsuhiro ichiharaAtsuhiro Ichihara,yuki kaneshiroYuki Kaneshiro,tomoko takemitsuTomoko Takemitsu,mariyo sakodaMariyo Sakoda,tsutomu nakagawaTsutomu Nakagawa,akira nishiyamaAkira Nishiyama,hiroshi kawachiHiroshi Kawachi,fujio shimizuFujio Shimizu,tadashi inagamiTadashi Inagami,

    Prorenin is activated without proteolysis by binding of prorenin receptor to the pentameric "handle region" (HR) of prorenin prosegment. It was hypothesized that such activation occurs in the kidneys of hypertensive rats and causes tissue renin-angiotensin system (RAS) activation and end-organ damage. Because the HR's binding to its binding protein made the adjacent tetrameric "gate region" (GR) accessible to its specific antibody, immunohistochemistry of the GR was performed to test the hypothesis. Methods also were devised specifically to inhibit the nonproteolytic activation by the decapeptide corresponding to the HR as a decoy. Immunohistochemistry of the GR demonstrated that the majority of nonproteolytically activated prorenin is present in podocytes of the kidneys from stroke-prone spontaneously hypertensive rats, in which activation of renal tissue RAS, proteinuria, and glomerulosclerosis occurred. Continuous subcutaneous administration of the HR decoy peptide completely inhibited both nonproteolytic activation of tissue prorenin and activation of tissue RAS without affecting circulating RAS or arterial pressure and significantly attenuated the development and progression of proteinuria and glomerulosclerosis. These studies clearly demonstrated that nonproteolytic activation of prorenin in glomeruli is critically involved in renal tissue RAS activation, leading to renal damage in hypertensive animals.

    Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage. Publishing Authors By Initials

    a ichiharaA Ichihara,y kaneshiroY Kaneshiro,t takemitsuT Takemitsu,m sakodaM Sakoda,t nakagawaT Nakagawa,a nishiyamaA Nishiyama,h kawachiH Kawachi,f shimizuF Shimizu,t inagamiT Inagami,

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    Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Journal of the American Society of Nephrology : JA

    VOLUME: 17

    Page Numbers: 2495-503

    Journal Abbreviation:

    ISSN: 1046-6673

    DAY: 2

    MONTH: 08

    YEAR: 2006

    Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage. Information

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    LANGUAGE: eng

    NlmUniqueID: 9013836

    Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage. Keywords Mesh Terms:

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    Grant and Affiliation Information for Contribution of nonproteolytically activated prorenin in glomeruli to hypertensive renal damage.

    AFFILIATION: Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. atzichi@sc.itc.keio.ac.jp

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Am Soc Nephrol

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