Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells.
Mitochondrial damage with release of cytochrome c is implicated in cell death signalling pathways. To examine mitochondrial function in apoptotic cells, we applied high-resolution respirometry to human leukemia cells arrested in the G1- and S-phase by exposure to the glucocorticoid dexamethasone and nucleotide analogue gemcitabine. At 30% apoptosis, opposite effects were observed on respiratory capacity (71% and 131% of controls, respectively). These changes correlated with alterations in cell size, cytosolic, and mitochondrial marker enzymes. Mitochondrial ATP production and membrane potential were maintained in all treatments, as deduced from high respiratory uncoupling control ratios (UCR). Bcl-2 over-expression did not prevent apoptosis after gemcitabine-treatment, but protected dexamethasone-treated cells from apoptosis, without fully preventing the decline of respiration and cell size. These results, therefore, provide conclusive evidence that alterations in respiratory capacity and enzyme activities per cell are mainly caused by opposite changes in cell size, occurring upon cell cycle arrest triggered by dexamethasone and gemcitabine in the early phase of apoptosis.
Renner
Kathrin
K
Tyrolean Cancer Research Institute, Innrain 66, A-6020 Innsbruck, Austria.
Amberger
Albert
A
Konwalinka
Günther
G
Kofler
Reinhard
R
Gnaiger
Erich
E
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D018816:Genes, cdc / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D019253:Proto-Oncogene Proteins c-bcl-2; D003841:Deoxycytidine; D003907:Dexamethasone; D000093542:Gemcitabine