Antioxidant defence systems and generation of reactive oxygen species in osteosarcoma cells with defective mitochondria: effect of selenium

Marta Wojewoda; Jerzy Duszyński; Joanna Szczepanowska

doi:10.1016/j.bbabio.2010.01.035

Antioxidant defence systems and generation of reactive oxygen species in osteosarcoma cells with defective mitochondria: effect of selenium

Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):890-6. doi: 10.1016/j.bbabio.2010.01.035. Epub 2010 Feb 4.

Authors

Marta Wojewoda¹, Jerzy Duszyński, Joanna Szczepanowska

Affiliation

¹ Nencki Institute of Experimental Biology, Department of Biochemistry, Pasteura 3, 02-093 Warsaw, Poland.

PMID: 20138159
DOI: 10.1016/j.bbabio.2010.01.035

Abstract

Mitochondrial diseases originate from mutations in mitochondrial or nuclear genes encoding for mitochondrial proteome. Neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) syndrome is associated with the T8993G transversion in ATP6 gene which results in substitution at the very conservative site in the subunit 6 of mitochondrial ATP synthase. Defects in the mitochondrial respiratory chain and the ATPase are considered to be accompanied by changes in the generation of reactive oxygen species (ROS). This study aimed to elucidate effects of selenium on ROS and antioxidant system of NARP cybrid cells with 98% of T8993G mutation load. We found that selenium decreased ROS generation and increased the level and activity of antioxidant enzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). Therefore, we propose selenium to be a promising therapeutic agent not only in the case of NARP syndrome but also other diseases associated with mitochondrial dysfunctions and oxidative stress.

MeSH terms

Antioxidants / metabolism*
Antioxidants / pharmacology
Catalase / metabolism
Cell Line, Tumor
DNA, Mitochondrial / genetics
Humans
Hybrid Cells
Mitochondria / drug effects*
Mitochondria / genetics
Mitochondria / metabolism*
Mitochondrial Myopathies / drug therapy
Mitochondrial Myopathies / genetics
Mitochondrial Myopathies / metabolism
Mitochondrial Proton-Translocating ATPases / genetics
Mutation, Missense
NF-E2-Related Factor 2 / metabolism
Osteosarcoma / drug therapy*
Osteosarcoma / metabolism*
Reactive Oxygen Species / metabolism*
Retinitis Pigmentosa / drug therapy
Retinitis Pigmentosa / genetics
Retinitis Pigmentosa / metabolism
Selenium / pharmacology*
Superoxide Dismutase / metabolism
Syndrome
Thioredoxin-Disulfide Reductase / metabolism

Substances

Antioxidants
DNA, Mitochondrial
MT-ATP6 protein, human
NF-E2-Related Factor 2
NFE2L2 protein, human
Reactive Oxygen Species
Catalase
Superoxide Dismutase
Thioredoxin-Disulfide Reductase
Mitochondrial Proton-Translocating ATPases
Selenium

Supplementary concepts

Neuropathy ataxia and retinitis pigmentosa