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

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{{Publication
{{Publication
|title=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
|title=Lee WK, 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:F27-39.
|authors=Lee W-K, Bork U, Gholamrezaei F, Tevenod F  
|info=[http://www.ncbi.nlm.nih.gov/pubmed/15339793 PMID: 15339793 Open Access]
|authors=Lee WK, Bork U, Gholamrezaei F, Thevenod F
|year=2005
|year=2005
|journal=American Journal of Physiology-Renal Physiology
|journal=Am J Physiol Renal Physiol
|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 (EC50 ~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 (PO43– or H2O2+Ca2+). 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]
}}
}}
{{Labeling
{{Labeling
|injuries=Cancer; Apoptosis; Cytochrome c
|organism=Rat
|organism=Rat
|tissues=Kidney
|tissues=Kidney
|enzymes=Complex IV; Cytochrome c Oxidase, Inner mtMembrane Transporter
|preparations=Intact cells, Isolated mitochondria
|topics=Respiration; OXPHOS; ETS Capacity
|enzymes=Complex IV;cytochrome c oxidase, Inner mt-membrane transporter
|injuries=Cell death
|couplingstates=OXPHOS
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
}}
}}

Latest revision as of 13:56, 24 March 2015

Publications in the MiPMap
Lee WK, 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:F27-39.

» PMID: 15339793 Open Access

Lee WK, Bork U, Gholamrezaei F, Thevenod F (2005) Am J Physiol Renal Physiol

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:Cell death  Organism: Rat  Tissue;cell: Kidney  Preparation: Intact cells, Isolated mitochondria  Enzyme: Complex IV;cytochrome c oxidase, Inner mt-membrane transporter 

Coupling state: OXPHOS 

HRR: Oxygraph-2k