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

Lodovica Vergani, Maura Floreani, Aaron Russell, Mara Ceccon, Eleonora Napoli, Anna Cabrelle, Lucia Valente, Federica Bragantini, Bertrand Leger, Federica Dabbeni-Sala

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3646-3656
Number of pages11
JournalEuropean Journal of Biochemistry
Volume271
Issue number18
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

Keywords

  • 143 ρ cells
  • A549 ρ cells
  • Antioxidant defences
  • Reactive oxygen species
  • Rhabdomyosarcoma ρ cells

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Vergani, L., Floreani, M., Russell, A., Ceccon, M., Napoli, E., Cabrelle, A., Valente, L., Bragantini, F., Leger, B., & Dabbeni-Sala, F. (2004). Antioxidant defences and homeostasis of reactive oxygen species in different human mitochondrial DNA-depleted cell lines. European Journal of Biochemistry, 271(18), 3646-3656. https://doi.org/10.1111/j.1432-1033.2004.04298.x