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Difference between revisions of "Lee 2005 Am J Physiol Renal Physiol"

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|year=2005
|year=2005
|journal=American Journal of Physiology-Renal Physiology
|journal=American Journal of Physiology-Renal Physiology
|abstract=Cd<sup>2+</sup> induces apoptosis of kidney proximal tubule (PT) cells. Mitochondria play a pivotal role in toxic compound-induced apoptosis by releasing cytochrome c. Our objective was to investigate the mechanisms underlying Cd<sup>2+</sup>-induced cytochrome c release from mitochondria in rat PT cells. Using Hoechst 33342 or MTT assay, 10 µM Cd<sup>2+</sup> induced ~5–10% apoptosis in PT cells at 6 and 24 h, which was associated with cytochrome c and apoptosis-inducing factor release at 24 h only. This correlated with previously described maximal intracellular Cd<sup>2+</sup> concentrations at 24 h, suggesting that elevated Cd<sup>2+</sup> may directly induce mitochondrial liberation of proapoptotic factors. Indeed, Cd<sup>2+</sup> caused swelling of energized isolated kidney cortex mitochondria (ECCd<sub>50</sub> ~9 µM) and cytochrome c release, which were independent of permeability transition pore (PTP) opening since PTP inhibitors cyclosporin A or bongkrekic acid had no effect. On the contrary, Cd<sup>2+</sup> inhibited swelling and cytochrome c release induced by PTP openers (POCd<sub>43</sub>– or H<sub>2</sub>O<sub>2</sub>+Cd<sup>2+</sup>). The mitochondrial Cd<sup>2+</sup> uniporter (MCU) played a key role in mitochondrial damage: 1) MCU inhibitors (La3+, ruthenium red, Ru360) prevented swelling and cytochrome c release; and 2) ruthenium red attenuated Cd<sup>2+</sup> inhibition of PO43–-induced swelling. Using the Cd<sup>2</sup>-sensitive fluorescent indicator FluoZin-1, Cd<sup>2+</sup> was also taken up by mitoplasts. The aquaporin inhibitor AgNO3 abolished Cd2+-induced swelling of mitoplasts. This could be partially mediated by activation of the mitoplast-enriched water channel aquaporin-8. Thus cytosolic Cd<sup>2+</sup> concentrations exceeding a certain threshold may directly cause mitochondrial damage and apoptotic development by interacting with MCU and water channels in the inner mitochondrial membrane.
|abstract=Cd<sup>2+</sup> induces apoptosis of kidney proximal tubule (PT) cells. Mitochondria play a pivotal role in toxic compound-induced apoptosis by releasing cytochrome c. Our objective was to investigate the mechanisms underlying Cd<sup>2+</sup>-induced cytochrome c release from mitochondria in rat PT cells. Using Hoechst 33342 or MTT assay, 10 µM Cd<sup>2+</sup> induced ~5–10% apoptosis in PT cells at 6 and 24 h, which was associated with cytochrome c and apoptosis-inducing factor release at 24 h only. This correlated with previously described maximal intracellular Cd<sup>2+</sup> concentrations at 24 h, suggesting that elevated Cd<sup>2+</sup> may directly induce mitochondrial liberation of proapoptotic factors. Indeed, Cd<sup>2+</sup> caused swelling of energized isolated kidney cortex mitochondria (ECCd<sub>50</sub> ~9 µM) and cytochrome c release, which were independent of permeability transition pore (PTP) opening since PTP inhibitors cyclosporin A or bongkrekic acid had no effect. On the contrary, Cd<sup>2+</sup> inhibited swelling and cytochrome c release induced by PTP openers (POCd<sub>43</sub>– or H<sub>2</sub>O<sub>2</sub>+Cd<sup>2+</sup>). The mitochondrial Cd<sup>2+</sup> uniporter (MCU) played a key role in mitochondrial damage: 1) MCU inhibitors (La3+, ruthenium red, Ru360) prevented swelling and cytochrome c release; and 2) ruthenium red attenuated Cd<sup>2+</sup> inhibition of PO43–-induced swelling. Using the Cd<sup>2</sup>-sensitive fluorescent indicator FluoZin-1, Cd<sup>2+</sup> was also taken up by mitoplasts. The aquaporin inhibitor AgNO<sub>3</sub> abolished Cd2+-induced swelling of mitoplasts. This could be partially mediated by activation of the mitoplast-enriched water channel aquaporin-8. Thus cytosolic Cd<sup>2+</sup> concentrations exceeding a certain threshold may directly cause mitochondrial damage and apoptotic development by interacting with MCU and water channels in the inner mitochondrial membrane.
|keywords=Cadmium, Aquaporin, Apoptosis-inducing factor, Cyclosporin A
|keywords=Cadmium, Aquaporin, Apoptosis-inducing factor, Cyclosporin A
|info=[http://www.ncbi.nlm.nih.gov/pubmed/15339793 PMID: 15339793]
|info=[http://www.ncbi.nlm.nih.gov/pubmed/15339793 PMID: 15339793]

Revision as of 08:41, 4 October 2010

Publications in the MiPMap
Lee W-K, Bork U, Gholamrezaei F, Thévenod F (2005) Cd2+-induced cytochrome c release in apoptotic proximal tubule cells: role of mitochondrial permeability transition pore and Ca2+ uniporter. Am. J. Physiol. Renal Physiol. 288: F27-F39

» PMID: 15339793

Lee W-K, Bork U, Gholamrezaei F, Tevenod F (2005) American Journal of Physiology-Renal Physiology

Abstract: Cd2+ induces apoptosis of kidney proximal tubule (PT) cells. Mitochondria play a pivotal role in toxic compound-induced apoptosis by releasing cytochrome c. Our objective was to investigate the mechanisms underlying Cd2+-induced cytochrome c release from mitochondria in rat PT cells. Using Hoechst 33342 or MTT assay, 10 µM Cd2+ induced ~5–10% apoptosis in PT cells at 6 and 24 h, which was associated with cytochrome c and apoptosis-inducing factor release at 24 h only. This correlated with previously described maximal intracellular Cd2+ concentrations at 24 h, suggesting that elevated Cd2+ may directly induce mitochondrial liberation of proapoptotic factors. Indeed, Cd2+ caused swelling of energized isolated kidney cortex mitochondria (ECCd50 ~9 µM) and cytochrome c release, which were independent of permeability transition pore (PTP) opening since PTP inhibitors cyclosporin A or bongkrekic acid had no effect. On the contrary, Cd2+ inhibited swelling and cytochrome c release induced by PTP openers (POCd43– or H2O2+Cd2+). The mitochondrial Cd2+ uniporter (MCU) played a key role in mitochondrial damage: 1) MCU inhibitors (La3+, ruthenium red, Ru360) prevented swelling and cytochrome c release; and 2) ruthenium red attenuated Cd2+ inhibition of PO43–-induced swelling. Using the Cd2-sensitive fluorescent indicator FluoZin-1, Cd2+ was also taken up by mitoplasts. The aquaporin inhibitor AgNO3 abolished Cd2+-induced swelling of mitoplasts. This could be partially mediated by activation of the mitoplast-enriched water channel aquaporin-8. Thus cytosolic Cd2+ concentrations exceeding a certain threshold may directly cause mitochondrial damage and apoptotic development by interacting with MCU and water channels in the inner mitochondrial membrane. Keywords: Cadmium, Aquaporin, Apoptosis-inducing factor, Cyclosporin A


Labels:

Stress:Cancer; Apoptosis; Cytochrome c"Cancer; Apoptosis; Cytochrome c" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Rat  Tissue;cell: Kidney 

Enzyme: Complex IV; Cytochrome c Oxidase"Complex IV; Cytochrome c Oxidase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property., Inner mtMembrane Transporter"Inner mtMembrane Transporter" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 


HRR: Oxygraph-2k