Loss of thioredoxin function in retinas of mice overexpressing amyloid β

Folami Lamoke Powell, Guido Ripandelli, Scott Webster, Annalisa Montemari, Annamaria Maraschi, Pamela Moore Martin, Dennis M. Marcus, Gregory I Liou, Manuela Bartoli

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Amyloid β peptides (Aβ) have been implicated in the pathogenesis of age-related macular degeneration (ARMD) and glaucoma. In this study, retinas of mice overexpressing Aβ (Tg) were compared to those of wild-type mice (Wt) and analyzed for oxidative stress parameters. We observed a progressive decrease in all retinal cell layers, which was significantly greater in Tg mice at 14 months and culminated in loss of the outer retina at 18 months of age. We also observed higher levels of reactive oxygen species, glial fibrillary acidic protein, and hydroperoxide in Tg versus Wt mice (14 months). These effects were associated with phosphorylation/activation of the apoptosis signal kinase 1 and the p38 mitogen-activated kinase. Western blotting analysis revealed progressive increases in the levels of thioredoxin 1 and thioredoxin inhibitory protein in Tg compared to Wt mice. No changes were observed in the levels of thioredoxin reductase 1 (TrxR1); however, measurements of TrxR1 activity showed a 42.7±8% reduction in Tg mice versus Wt at 14 months of age. Our data suggest that Aβ-mediated retinal neurotoxicity involves impairment of the thioredoxin system and enhanced oxidative stress, potentially implicating this mechanism in the pathogenesis of ARMD and glaucoma.

Original languageEnglish (US)
Pages (from-to)577-588
Number of pages12
JournalFree Radical Biology and Medicine
Volume53
Issue number3
DOIs
StatePublished - Aug 1 2012

Fingerprint

Thioredoxins
Thioredoxin Reductase 1
Amyloid
Retina
Oxidative stress
Phosphotransferases
Phosphorylation
Glial Fibrillary Acidic Protein
Mitogens
Hydrogen Peroxide
Reactive Oxygen Species
Chemical activation
Cells
Macular Degeneration
Apoptosis
Glaucoma
Oxidative Stress
Proteins
Western Blotting

Keywords

  • Amyloid β
  • Antioxidants
  • Apoptosis signaling kinase-1
  • Free radicals
  • Oxidative stress
  • Retinal degeneration
  • Thioredoxin
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Loss of thioredoxin function in retinas of mice overexpressing amyloid β. / Powell, Folami Lamoke; Ripandelli, Guido; Webster, Scott; Montemari, Annalisa; Maraschi, Annamaria; Martin, Pamela Moore; Marcus, Dennis M.; Liou, Gregory I; Bartoli, Manuela.

In: Free Radical Biology and Medicine, Vol. 53, No. 3, 01.08.2012, p. 577-588.

Research output: Contribution to journalArticle

Powell, Folami Lamoke ; Ripandelli, Guido ; Webster, Scott ; Montemari, Annalisa ; Maraschi, Annamaria ; Martin, Pamela Moore ; Marcus, Dennis M. ; Liou, Gregory I ; Bartoli, Manuela. / Loss of thioredoxin function in retinas of mice overexpressing amyloid β. In: Free Radical Biology and Medicine. 2012 ; Vol. 53, No. 3. pp. 577-588.
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