Effect of celecoxib on Ca2+ fluxes and proliferation in MDCK renal tubular cells |
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Authors: | Wang J L Lin K L Chen W C Chou C T Huang C J Liu C S Hsieh C H Chang C H Huang J K Chang H T Liu S I Hsu S S Jan C R |
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Institution: | Department of Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. |
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Abstract: | The effect of celecoxib on renal tubular cells is largely unexplored. In Madin Darby canine kidney (MDCK) cells, the effect of celecoxib on intracellular CaCa2+ concentration (Ca2+]i) and proliferation was examined by using the Ca(2 +)-sensitive fluorescent dye fura-2 and the viability detecting fluorescent dye tetrazolium, respectively. Celecoxib (> or =1 micro M) caused an increase of CaCa2+]i in a concentration-dependent manner. Celecoxib-induced CaCa2+]i increase was partly reduced by removal of extracellular CaCa2+. Celecoxib-induced CaCa2+ influx was independently suggested by MnCa2+ influx-induced fura-2 fluorescence quench. In Ca(2 +)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2 +)-ATPase, caused a monophasic CaCa2+]i increase, after which celecoxib only induced a tiny CaCa2+]i increase; conversely, pretreatment with celecoxib completely inhibited thapsigargin-induced CaCa2+]i increases. U73122, an inhibitor of phospholipase C, abolished ATP (but not celecoxib)-induced CaCa2+]i increases. Overnight incubation with 1 or 10 micro M celecoxib decreased cell viability by 80% and 100%, respectively. These data indicate that celecoxib evokes a CaCa2+]i increase in renal tubular cells by stimulating both extracellular CaCa2+ influx and intracellular CaCa2+ release and is highly toxic to renal tubular cells in vitro. |
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