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Ouabain stimulates both proliferation and apoptosis in renal epithelial cells from patients with autosomal dominant polycystic kidney disease.
Author(s) -
Blanco Gustavo,
Nguyen AnhNguyet
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.1157.6
Subject(s) - mapk/erk pathway , cancer research , microbiology and biotechnology , ouabain , kinase , medicine , endocrinology , epidermal growth factor , biology , cell growth , apoptosis , autosomal dominant polycystic kidney disease , phosphorylation , polycystic kidney disease , kidney , chemistry , receptor , biochemistry , organic chemistry , sodium
The hormone ouabain binds to its receptor, the Na,K‐ATPase to regulate cell growth and survival. We have studied the effect and intracellular signaling pathways of ouabain in the proliferation and apoptosis of epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD cells). Physiological levels of ouabain (3 nM) stimulated growth in ADPKD cells. This required the integrity of cell caveolae, and phosphorylation of caveolin‐1. In addition ouabain effect involved phosphorylation of the kinase Src and the epidermal growth factor receptor (EGFR). Downstream signaling of ouabain included activation of B‐Raf and the kinases, MEK and ERK. ERK phosphorylation resulted in translocation of the kinase to the cell nucleus and down‐regulation of expression of the cyclin‐dependent kinase inhibitors, p21 and p27. On the other hand, ouabain also enhanced apoptosis of ADPKD cells through activation of caspase 3. Altogether, these results suggest that ouabain activates both proliferation and programmed cell death, affecting the balance between these processes to favor ADPKD cell growth. Uncontrolled cell growth and abnormal rate of apoptosis play an essential role in kidney cyst formation and development in ADPKD. Therefore, ouabain is an important factor with the potential to enhance progression of the disease. [Supported by NIH grant HD043044 and a grant from the PKD Foundation].