The contribution of DNA repair and antioxidants in determining cell type-specific resistance to oxidative stress

Stuart G. Jarrett, Julie Albon, Mike Boulton

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The aims of this study were; (i) to elucidate the mechanisms involved in determining cell type-specific responses to oxidative stress and (ii) to test the hypothesis that cell types which are subjected to high oxidative burdens in vivo, have greater oxidative stress resistance. Cultures of the retinal pigment epithelium (RPE), corneal fibroblasts, alveolar type II epithelium and skin epidermal cells were studied. Cellular sensitivity to H2O2 was determined by the MTT assay. Cellular antioxidant status (CuZnSOD, MnSOD, GPX, CAT) was analyzed with enzymatic assays and the susceptibility and repair capacities of nuclear and mitochondrial genomes were assessed by QPCR. Cell type-specific responses to H2O2 were observed. The RPE had the greatest resistance to oxidative stress (P <0.05; compared to all other cell types) followed by the corneal fibroblasts (P <0.05; compared to skin and lung cells). The oxidative tolerance of the RPE coincided with greater CuZnSOD, GPX and CAT enzymatic activity (P <0.05; compared to other cells). The RPE and corneal fibroblasts both had up-regulated nDNA repair post-treatment (P <0.05; compared to all other cells). In summary, variations in the synergistic interplay between enzymatic antioxidants and nDNA repair have important roles in influencing cell type-specific vulnerability to oxidative stress. Furthermore, cells located in highly oxidizing microenvironments appear to have more efficient oxidative defence and repair mechanisms.

Original languageEnglish (US)
Pages (from-to)1155-1165
Number of pages11
JournalFree Radical Research
Volume40
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Oxidative stress
Retinal Pigments
DNA Repair
Oxidative Stress
Repair
Fibroblasts
Antioxidants
DNA
Retinal Pigment Epithelium
Assays
Skin
Genes
Mitochondrial Genome
Enzyme Assays
Epithelium
Lung

Keywords

  • Aging
  • Antioxidant enzymes
  • DNA repair
  • Oxidative DNA damage
  • Oxidative stress
  • Post-mitotic cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

The contribution of DNA repair and antioxidants in determining cell type-specific resistance to oxidative stress. / Jarrett, Stuart G.; Albon, Julie; Boulton, Mike.

In: Free Radical Research, Vol. 40, No. 11, 11.2006, p. 1155-1165.

Research output: Contribution to journalArticle

Jarrett, Stuart G. ; Albon, Julie ; Boulton, Mike. / The contribution of DNA repair and antioxidants in determining cell type-specific resistance to oxidative stress. In: Free Radical Research. 2006 ; Vol. 40, No. 11. pp. 1155-1165.
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