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Release of renal dipeptidase from Glycosylphosphatidylinositol anchor by insulin-triggered phospholipase c/intracellular Ca2+

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Abstract

Glycosylphosphatidylinositol (GPI) anchored proteins appear to be released from the plasma membrane due to various extracellular stimuli. To determine the signaling pathway from insulin to GPI-protein, the release of GPI-renal dipeptidase (RDPase, EC 3.4.13.19) from porcine proximal tubules, stimulated by insulin, was explored. Insulin stimulated the release of RDPase in a concentration-dependent manner (half maximal release at 0.58 nM), which peaked at 10– 20 min. Western blot analysis, with antibody against the cross-reacting determinant (CRD), revealed that RDPase was released by a GPI-specific phospholipase C (GPI-PLC), and was shown to be Ca2+-dependent. A PI-PLC inhibitor, U73122, effectively blocked the effect of insulin on the release of RDPase, suggesting insulin is associated with an intracellular PI-PLC. Insulin treatment increased the production of intracellular Ca2+ from porcine proximal tubules. Intracellular Ca2+ coupled with insulin, facilitated the releases of RDPase, an inhibitor of inositol trisphosphate-dependent Ca2+ from the endoplasmic reticulum, and a Ca2+ channel blocker that blocked the effect of insulin. Taken together, these results suggest that insulin, in part, may activate a GPI-PLC, via PI-PLC/intracellular Ca2+, which may consequently stimulate the release of RDPase.

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Authors and Affiliations

  1. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, 300 Yongbong-dong, Buk-gu, 500-757, Kwangju, Gwangju, Korea

    Hyun Joong Yoon, Sung Wook Park & Haeng Soon Park

  2. Department of Biology, College of natural Science, Chonnam National University, 500-757, Gwangju, Korea

    Hwanghee Blaise Lee & Shun Young Im

  3. Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, Leeds, UK

    Nigel M. Hooper

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  1. Hyun Joong Yoon
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  2. Sung Wook Park
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  3. Hwanghee Blaise Lee
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  4. Shun Young Im
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  5. Nigel M. Hooper
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  6. Haeng Soon Park
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Correspondence to Haeng Soon Park.

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Yoon, H.J., Park, S.W., Lee, H.B. et al. Release of renal dipeptidase from Glycosylphosphatidylinositol anchor by insulin-triggered phospholipase c/intracellular Ca2+ . Arch Pharm Res 30, 608–615 (2007). https://doi.org/10.1007/BF02977656

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  • DOI: https://doi.org/10.1007/BF02977656

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