Proteomic analysis of brain protein expression levels in NF-κβ p50 -/- homozygous knockout mice

Joshua B. Owen, Wycliffe O. Opii, Charles Ramassamy, William M. Pierce, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Abstract: The role of nuclear factor kappa B (NF-κB) in oxidative stress, and most recently in pro- and anti-apoptotic-related mechanistic pathways, has well been established. Because of the dual nature of NF-κB, the wide range of genes it regulates and the plethora of stimuli that activate it, various studies addressing the functional role of NF-κB proteins have resulted in a number of differing findings. The present study examined the effect of a stimulus-free environment on the frontal cortex of mice brain with the p50 subunit of NF-κB knocked out p50 (-/-). Homozygous p50 mice knockout (KO) and wild type (WT) were used, and at 7-9 weeks they were sacrificed and various brain regions dissected. We analyzed the levels of oxidation in the frontal cortex of both the p50 (-/-) and WT mice. There was a significant reduction in the levels of protein-bound 4-hydroxynonenal (HNE) [a lipid peroxidation product], 3-nitrotyrosine (3NT), and protein carbonyls in the p50 (-/-) mice when compared to the WT. A proteomic profile analysis identified ATP synthase gamma chain, ubiquinol-cyt-C reductase, heat shock protein 10 (Hsp10), fructose bisphosphate aldolase C, and NADH-ubiquinone oxidoreductase as proteins whose expressions were significantly increased in the p50 (-/-) mice compared to the WT. With the reduction in the levels of oxidative stress and the increase in expression of key proteins in the p50 (-/-) brain, this study suggests that the p50 subunit can potentially be targeted for the development of therapeutic interventions in disorders in which oxidative stress plays a key role.

Original languageEnglish
Pages (from-to)22-30
Number of pages9
JournalBrain Research
Volume1240
DOIs
StatePublished - Nov 13 2008

Bibliographical note

Funding Information:
This work was supported in part by grants from NIH to D.A.B. [AG-10836; AG-05119].

Keywords

  • NF-kappa B
  • Oxidative stress
  • Proteomics
  • p50 knockout mice

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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