Alterations of Na/K-ATPase function in caveolin-1 knockout cardiac fibroblasts |
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Authors: | Luis EM Quintas Sandrine V Pierre Yan Bai Xiaochen Liu |
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Institution: | a Department of Physiology and Pharmacology, College of Medicine, University of Toledo, 3035 Arlington Avenue, Toledo, OH 43614-5804, USA b Laboratório de Farmacologia Bioquímica e Molecular, ICB, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco J, sala J-17 - CCS, Ilha do Fundão, Rio de Janeiro, Brazil c Department of Pediatrics, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China |
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Abstract: | Recent studies have demonstrated that the Na+/K+-ATPase is not only an ion pump, but also a membrane receptor that confers the ligand-like effects of cardiotonic steroids (CTS) such as ouabain on protein kinases and cell growth. Because CTS have been implicated in cardiac fibrosis, this study examined the role of caveolae in the regulation of Na+/K+-ATPase function and CTS signaling in cardiac fibroblasts. In cardiac fibroblasts prepared from wild-type and caveolin-1 knockout Cav-1(−/−)] mice, we found that the absence of caveolin-1 did not affect total cellular amount or surface expression of Na+/K+-ATPase α1 subunit. However, it did increase ouabain-sensitive 86Rb+ uptake. While knockout of caveolin-1 increased basal activities of Src and ERK1/2, it abolished the activation of these kinases induced by ouabain but not angiotensin II. Finally, ouabain stimulated collagen synthesis and cell proliferation in wild type but not Cav-1(−/−) cardiac fibroblasts. Thus, we conclude that caveolae are important for regulating both pumping and signal transducing functions of Na+/K+-ATPase. While depletion of caveolae increases the pumping function of Na+/K+-ATPase, it suppresses CTS-induced signal transduction, growth, and collagen production in cardiac fibroblasts. |
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Keywords: | Na+/K+-ATPase Caveolae Ouabain Cardiac fibrosis Digitalis signaling |
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