KMID : 0043320070300050608
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Archives of Pharmacal Research 2007 Volume.30 No. 5 p.608 ~ p.615
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Release of Renal Dipeptidase from Glycosylphosphatidylinositol Anchor by Insulin-Triggered Phospholipase C/Intracellular Ca2+
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Yoon Hyun-Joong
Park Sung-Wook Lee Hwang-Hee Im Shun-Young Hooper Nigel M. Park Haeng-Soon
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Abstract
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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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KEYWORD
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Glycosylphosphatidylinositol-Renal dipeptidase, Insulin, Intracellular Ca2+, Phophatidylinositol-specific phospholipase C, Glycosylphosphatidylinositol-specific phospholipase C
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