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Artículo

Mitochondrial aquaporin-8 knockdown in human hepatoma HepG2 cells causes ROS-induced mitochondrial depolarization and loss of viability

Marchissio, Maria JuliaIcon ; Frances, Daniel Eleazar AntonioIcon ; Carnovale, Cristina EsterIcon ; Marinelli, Raul AlbertoIcon
Fecha de publicación: 10/2012
Editorial: Elsevier Inc
Revista: Toxicology And Applied Pharmacology
ISSN: 0041-008X
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Biológicas

Resumen

Human aquaporin-8 (AQP8) channels facilitate the diffusional transport of H2O2 across membranes. Since AQP8 is expressed in hepatic inner mitochondrial membranes, we studied whether mitochondrial AQP8 (mtAQP8) knockdown in human hepatoma HepG2 cells impairs mitochondrial H2O2 release, which may lead to organelle dysfunction and cell death. We confirmed AQP8 expression in HepG2 inner mitochondrial membranes and found that 72 h after cell transfection with siRNAs targeting two different regions of the human AQP8 molecule, mtAQP8 protein specifically decreased by around 60% (pb0.05). Studies in isolated mtAQP8-knockdown mitochondria showed that H2O2 release, assessed by Amplex Red, was reduced by about 45% (pb0.05), an effect not observed in digitonin-permeabilized mitochondria. mtAQP8-knockdown cells showed an increase in mitochondrial ROS, assessed by dichlorodihydrofluorescein diacetate (+120%, pb0.05) and loss of mitochondrial membrane potential (−80%, pb0.05), assessed by tetramethylrhodamine-coupled quantitative fluorescence microscopy. The mitochondria-targeted antioxidant MitoTempol prevented ROS accumulation and dissipation of mitochondrial membrane potential. Cyclosporin A, a mitochondrial permeability transition pore blocker, also abolished the mtAQP8 knockdown-induced mitochondrial depolarization. Besides, the loss of viability in mtAQP8 knockdown cells verified by MTT assay, LDH leakage, and trypan blue exclusion test could be prevented by cyclosporin A. Our data on human hepatoma HepG2 cells suggest that mtAQP8 facilitates mitochondrial H2O2 release and that its defective expression causes ROS-induced mitochondrial depolarization via the mitochondrial permeability transition mechanism, and cell death.
Palabras clave: Mitochondria , Aquaporin-8 , Hydrogen Peroxide , Ros , Hepg2
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/15377
DOI: http://dx.doi.org/10.1016/j.taap.2012.08.005
URL: http://www.sciencedirect.com/science/article/pii/S0041008X1200347X
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Articulos(IFISE)
Articulos de INST.DE FISIOLOGIA EXPERIMENTAL (I)
Citación
Marchissio, Maria Julia; Frances, Daniel Eleazar Antonio; Carnovale, Cristina Ester; Marinelli, Raul Alberto; Mitochondrial aquaporin-8 knockdown in human hepatoma HepG2 cells causes ROS-induced mitochondrial depolarization and loss of viability; Elsevier Inc; Toxicology And Applied Pharmacology; 264; 2; 10-2012; 246-254
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