Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P67775 (alpha isoform)
 797 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In aged mice, the redox-regulated transcription factor nuclear factor-kappaB (NF-kappaB) becomes constitutively active in many tissues, as well as in cells of the hematopoietic system. This oxidative stress-induced activity promotes the production of a number of pro-inflammatory cytokines, which can contribute to the pathology of many disease states associated with aging. The administration to aged mice of agents capable of activating the alpha isoform of the peroxisome proliferator-activated receptor (PPARalpha) was found to restore the cellular redox balance, evidenced by a lowering of tissue lipid peroxidation, an elimination of constitutively active NF-kappaB, and a loss in spontaneous inflammatory cytokine production. Aged animals bearing a null mutation in PPARalpha failed to elicit these changes following treatment with PPARalpha activators, but remained responsive to vitamin E supplementation. Aged C57BL/6 mice were found to express reduced transcript levels of PPARalpha and the peroxisome-associated genes acyl-CoA oxidase and catalase. Supplementation of these aged mice with PPARalpha activators or with vitamin E caused elevations in these transcripts to levels seen in young animals. Our results suggest that PPARalpha and the genes under its control play a role in the evolution of oxidative stress excesses observed in aging.
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PMID:Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging. 983 30

Common mucosal immune responses were depressed in aged mice that were orally immunized with Haemophilus influenzae type b oligosaccharide conjugated to Diphtheria CRM197 protein (Hib-DT) vaccine using cholera toxin as the mucosal adjuvant. Both common mucosal and systemic humoral immune responses were also depressed in aged mice that were subcutaneously immunized with vaccine formulations containing Hib-DT plus 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Dietary supplementation of aged mice with either the antioxidant vitamin E, or with known activators of the alpha isoform of the peroxisome proliferator activated receptor (PPAR-alpha) was capable of restoring their mucosal and systemic humoral immune responses to mature adult levels, by both the oral and subcutaneous routes of immunization. These data support a hypothesis that some aspects of immunosenescence are due to dysregulations in cellular functions, and are not due to any irreversible defects in cellular components of the immune system.
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PMID:Enhancement of common mucosal immunity in aged mice following their supplementation with various antioxidants. 1073 95