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Protein Kinase C Activity and Cell Proliferation in Polycystic Kidney Disease
Author(s) -
Heiden Jennifer,
Siroky Brian,
Gooz Monika,
Komlosi Peter,
Bell Phillip Darwin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1177.4
Subject(s) - cilium , protein kinase c , polycystic kidney disease , microbiology and biotechnology , chemistry , medicine , cell growth , bapta , biology , endocrinology , kidney , kinase , intracellular , biochemistry
Polycystic kidney disease is associated with the loss of the structure/function of the primary cilia. Cilia regulate intracellular calcium concentration ([Ca 2+ ] i ), with the loss of cilia leading to an elevation in [Ca 2+ ] i . These studies examine whether this increase in [Ca 2+ ] i would lead to protein kinase C (PKC) activation and whether activated PKC would contribute to cell proliferation in polycystic kidney disease. Studies were performed in cilia (‐) and cilia (+) collecting duct cell lines, derived from the Tg737 orpk mouse. Cilia (‐) cells compared to cilia (+) cells displayed reduced cytosolic PKC content. There was also increased translocation of PKC to the plasma membrane in cilia (‐) cells, as assessed with a α‐PKC antibody and confocal microscopy. In other studies, cilia (‐) cells proliferated at a much higher rate than cilia (+) cells. Chronic treatment with 10 μM BAPTA‐AM, a Ca 2+ chelating agent, reduced the proliferation rate in cilia (‐) cells to a level comparable to cilia (+) cells. Importantly, inhibition of α‐PKC with Ro‐32‐0432, also abolished increased proliferation in cilia (‐) cells compared to cilia (+) cells. Thus, we suggest that there is Ca 2+ ‐dependent increased α‐PKC translocation in cilia (‐) cells and that elevated PKC activity contributes to the hyper‐proliferation and possibly cyst formation in this model of polycystic kidney disease.