Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Lee 2005 Am J Physiol Renal Physiol

From Bioblast
The printable version is no longer supported and may have rendering errors. Please update your browser bookmarks and please use the default browser print function instead.
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