title: Proteomic analysis of brain protein expression levels in NF-kappabeta p50 -/- homozygous knockout mice.
abstract: The role of nuclear factor kappa B (NF-kappaB) 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-kappaB, the wide range of genes it regulates and the plethora of stimuli that activate it, various studies addressing the functional role of NF-kappaB 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-kappaB 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.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Owen
authors.forename: Wycliffe O
authors.initials: WO
authors.lastname: Opii
authors.forename: Charles
authors.initials: C
authors.lastname: Ramassamy
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D007091:Image Processing, Computer-Assisted; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D040901:Proteomics; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000447:Aldehydes; D052002:NF-kappa B p50 Subunit; C002744:3-nitrotyrosine; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal