Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress

Nadiya M. Druzhyna, Scott B. Hollensworth, Mark Kelley, Glenn L. Wilson, Susan P. LeDoux

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Within the central nervous system (CNS), there is a differential susceptibility among cell types to certain pathological conditions believed to involve oxidative stress. Oligodendrocytes are extremely sensitive to oxidative stress, which correlates with a decreased ability to repair damage in mitochondrial DNA (mtDNA), as we have shown previously. To determine whether there is a causal relationship, studies were carried out to correct the deficit in repair of the oxidative damage in mtDNA in cultured oligodendrocytes. A vector containing a mitochondrial transport sequence (MTS) upstream of the sequence for human 8-oxoguanine-DNA glycosylase (OGG) was transfected into the cells. The efficiency of transfection and the localization of recombinant protein were determined by fluorescence microscopy and by Western blot analysis. Subsequent mtDNA repair studies, employing 100 μM menadione to produce reactive oxygen species, showed a significant enhancement in repair of oxidative lesions in mtDNA of MTS-OGG transfected oligodendrocytes compared with cells transfected with vector only. Experiments were also conducted to determine the effect of changing mtDNA repair capacity on menadione-induced apoptosis in oligodendrocytes. These experiments show that targeting the OGG repair enzyme to mitochondria reduces the release of cytochrome c from the intermitochondrial space and the activation of caspase 9 in oligodendrocytes after exposure to menadione. Therefore, targeting of DNA repair enzymes to mitochondria appears to be a viable approach for the protection of cells against some of the deleterious effects of oxidative stress.

Original languageEnglish
Pages (from-to)370-378
Number of pages9
JournalGLIA
Volume42
Issue number4
DOIs
StatePublished - Jun 1 2003

Fingerprint

Vitamin K 3
Oligodendroglia
Mitochondrial DNA
Mitochondria
Oxidative Stress
DNA Glycosylases
DNA Repair Enzymes
DNA Repair
Cytoprotection
Caspase 9
Cytochromes c
Fluorescence Microscopy
Recombinant Proteins
Transfection
Reactive Oxygen Species
Central Nervous System
Western Blotting
8-hydroxyguanine
Apoptosis

Keywords

  • Apoptosis
  • DNA damage
  • DNA repair
  • Reactive oxygen species

ASJC Scopus subject areas

  • Immunology

Cite this

Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress. / Druzhyna, Nadiya M.; Hollensworth, Scott B.; Kelley, Mark; Wilson, Glenn L.; LeDoux, Susan P.

In: GLIA, Vol. 42, No. 4, 01.06.2003, p. 370-378.

Research output: Contribution to journalArticle

Druzhyna, Nadiya M. ; Hollensworth, Scott B. ; Kelley, Mark ; Wilson, Glenn L. ; LeDoux, Susan P. / Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress. In: GLIA. 2003 ; Vol. 42, No. 4. pp. 370-378.
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