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• W2045528996 abstract "Cyclosporine (CsA) has been reported to disrupt Ca2+ efflux from mitochondria, which suggests that CsA interference with Ca2+ homeostasis may be related to its nephrotoxicity. Therefore, the purpose of this study was (1) to determine intracellular free Ca2+ concentration ([Ca2+]i) and mitochondrial free Ca2+ concentration ([Ca2+]m) after primary cultures of rat renal cortical epithelial cells were exposed to cytotoxic concentrations of CsA; and (2) to explore the role of disruption of intracellular and mitochondrial Ca2+ homeostasis in CsA-induced cytotoxicity. [Ca2+]i in single kidney cells was examined by digitized fluorescence imaging (DFI) of the Ca2+ fluorescent probe, fura-2, and [Ca2+]m in single cells was observed by DFI of fura-2 entrapped in mitochondria after selective permeabilization of plasma membrane and other non-mitochondrial organelles by digitonin. Mitochondrial membrane potential (ΔΨ) in single kidney cells was examined by rhodamine 123 (Rh-123) with DFI. Intracellular ATP in kidney cells was determined by a HPLC method. CsA resulted in an elevation in [Ca2+]i and [Ca2+]m, dissipation of ΔΨ and depletion of ATP in a dose- and time-dependent manner. The elevation of [Ca2+]i and [Ca2+]m and depletion of ATP preceded CsA-induced cytotoxicity in kidney cells as measured by lactate dehydrogenase (LDH) leakage. We conclude that CsA-induced alterations in mitochondrial Ca2+ homeostasis and a subsequent loss of energy supply may play a key role in CsA-induced cytotoxicity in primary cultures of rat renal cortical epithelial cells." @default.
• W2045528996 created "2016-06-24" @default.
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• W2045528996 date "1995-01-01" @default.
• W2045528996 modified "2023-09-23" @default.
• W2045528996 title "Mitochondrial Ca2+ overload in primary cultures of rat renal cortical epithelial cells by cytotoxic concentrations of cyclosporine: a digitized fluorescence imaging study" @default.
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• W2045528996 doi "https://doi.org/10.1016/0300-483x(94)02901-6" @default.
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