Cadmium toxicity toward caspase-independent apoptosis through the mitochondria-calcium pathway in mtDNA-depleted cells
| Autor: | Yau-Huei Wei, Chwen Ming Shih, Sheng Wei Hsu, Chien Ju Lin, Yung Luen Shih, Wei Li Chen, Sheng Hao Wang, Mei Tsu Lee |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Programmed cell death
Caspase 3 Apoptosis Mitochondrion DNA Mitochondrial General Biochemistry Genetics and Molecular Biology Membrane Potentials History and Philosophy of Science Cell Line Tumor Humans Respiratory function Calcium Signaling Enzyme Inhibitors Inner mitochondrial membrane Caspase biology Caspase-Independent Apoptosis General Neuroscience Cell Polarity Caspase Inhibitors Cell biology Mitochondria Caspases Mitochondrial Membranes biology.protein Gene Deletion Cadmium |
| Zdroj: | Annals of the New York Academy of Sciences. 1042 |
| ISSN: | 0077-8923 |
| Popis: | Mitochondria are believed to be integrators and coordinators of programmed cell death in addition to their respiratory function. Using mito- chondrial DNA (mtDNA)-depleted osteosarcoma cells ( 0 cells) as a cell model, we investigated the apoptogenic signaling pathway of cadmium (Cd) under a condition of mitochondrial dysfunction. The apoptotic percentage was deter- mined to be around 58.0% after a 24-h exposure to 25 M Cd using flow cy- tometry staining with propidium iodine (PI). Pretreatment with Z-VAD-fmk, a broad-spectrum caspase inhibitor, failed to prevent apoptosis following Cd ex- posure. Moreover, Cd was unable to activate caspase 3 using DEVD-AFC as a substrate, indicating that Cd induced a caspase-independent apoptotic path- way in 0 cells. JC-1 staining demonstrated that mitochondrial membrane de- polarization was a prelude to apoptosis. On the other hand, the intracellular calcium concentration increased 12.5-fold after a 2-h exposure to Cd. More im- portantly, the apoptogenic activity of Cd was almost abolished by ruthenium red, a mitochondrial calcium uniporter blocker. This led us to conclude that mtDNA-depleted cells provide an alternative pathway for Cd to conduct caspase-independent apoptosis through a mitochondria-calcium mechanism. |
| Databáze: | OpenAIRE |
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