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Antioxidant defences and homeostasis of reactive oxygen species in different human mitochondrial DNA-depleted cell lines

journal contribution
posted on 01.01.2004, 00:00 authored by L Vergani, M Floreani, Aaron RussellAaron Russell, M Ceccon, E Napoli, A Cabrelle, L Valente, F Bragantini, B Leger, F Dabbeni-Sala
Three pairs of parental (ρ+) and established mitochondrial DNA depleted (ρ0) cells, derived from bone, lung and muscle were used to verify the influence of the nuclear background and the lack of efficient mitochondrial respiratory chain on antioxidant defences and homeostasis of intracellular reactive oxygen species (ROS). Mitochondrial DNA depletion significantly lowered glutathione reductase activity, glutathione (GSH) content, and consistently altered the GSH2 : oxidized glutathione ratio in all of the ρ0 cell lines, albeit to differing extents, indicating the most oxidized redox state in bone ρ0 cells. Activity, as well as gene expression and protein content, of superoxide dismutase showed a decrease in bone and muscle ρ0 cell lines but not in lung ρ0 cells. GSH peroxidase activity was four times higher in all three ρ0 cell lines in comparison to the parental ρ+, suggesting that this may be a necessary adaptation for survival without a functional respiratory chain. Taken together, these data suggest that the lack of respiratory chain prompts the cells to reduce their need for antioxidant defences in a tissue-specific manner, exposing them to a major risk of oxidative injury. In fact bone-derived ρ0 cells displayed the highest steady-state level of intracellular ROS (measured directly by 2',7'-dichlorofluorescin, or indirectly by aconitase activity) compared to all the other ρ+ and ρ0 cells, both in the presence or absence of glucose. Analysis of mitochondrial and cytosolic/iron regulatory protein-1 aconitase indicated that most ROS of bone ρ0 cells originate from sources other than mitochondria.

History

Journal

European journal of biochemistry

Volume

271

Issue

18

Pagination

3646 - 3656

Publisher

Blackwell Publishing Ltd

Location

Oxford, England

ISSN

1742-464X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2004, FEBS