7-Ketocholesterol and staurosporine induce opposite changes in intracellular pH,associated with distinct types of cell death in ECV304 cells |
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Authors: | Ghelli Anna Porcelli Anna Maria Zanna Claudia Rugolo Michela |
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Institution: | Dipartimento di Biologia Ev. Sp., Università di Bologna, Via Irnerio 42, 40126 Bologna, Italy. |
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Abstract: | Incubation of ECV304 cells with 7-ketocholesterol, a lipid component of oxidized low-density lipoproteins, caused a concentration- and time-dependent decrease in the number of viable cells. Other cholesterol oxides, 7 beta-hydroxycholesterol and 25-hydroxycholesterol, but not cholesterol, were only weakly cytotoxic. No evidence for activation of caspase-3 and -8, DNA laddering, or release of cytochrome c from mitochondria into the cytoplasm was obtained in 7-ketocholesterol-treated cells, indicating that cell death was not due to apoptosis. As a positive control for apoptosis, ECV304 cells were treated with staurosporine, which indeed caused significant activation of caspase-3 activity, DNA laddering, and cytochrome c release. Cellular morphology and actin cytoskeletal organization were distinctly different after exposure to the two drugs. Furthermore, staurosporine caused intracellular acidification, whereas 7-ketocholesterol induced a significant alkalinization, which was abolished by 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid. In conclusion, in ECV304 cells 7-ketocholesterol induces some typical hallmarks of necrotic cell death but not of apoptosis. |
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Keywords: | 7-ketocholesterol Staurosporine Apoptosis Necrosis Caspases Cytochrome c Cell morphology Intracellular pH |
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