title: Age-related NADH oxidase (arNOX)-catalyzed oxidative damage to skin proteins.
abstract: Age-related NADH oxidase (arNOX), a cell surface-located hydroquinone oxidase capable of superoxide generation, appears at age 30 and increases with age thereafter. The ectodomain of arNOX is shed from the cell surface into body fluids including sera and saliva where its activity was measured spectrophotometrically using a reduction of ferricytochrome c as a measure of superoxide generation. The autofluorescence of advanced glycation end products correlates with epidermal arNOX activity as well. To demonstrate protein cross-linking, a fluorescence-labeled analog of tyrosine, tyramine, that would react with proteins carrying arNOX-generated tyrosyl radicals was used. The assay demonstrated the potential for arNOX-induced oxidative damage (dityrosine formation) to human collagen and elastin and to other surface proteins of intact human embryo fibroblasts and frozen sections from epidermal punch biopsies. The findings support a role for arNOX as a major source of oxidative damage leading to cross-linking of skin proteins.
authors.affiliation: MorNuCo, Inc., Purdue Research Park, 1201 Cumberland Avenue, Ste. B, West Lafayette, IN, 47906, USA.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Meadows
authors.forename: D James
authors.initials: DJ
authors.lastname: Morré
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Morré
authors.forename: Zoe D
authors.initials: ZD
authors.lastname: Draelos
authors.forename: Dale
authors.initials: D
authors.lastname: Kern
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging; D001707:Biopsy, Needle; D003094:Collagen / Q000378:metabolism*; D045304:Cytochromes c / Q000737:chemistry; D004549:Elastin / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008297:Male; D008543:Melanins; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary; D012463:Saliva / Q000201:enzymology; D044967:Serum / Q000201:enzymology; D012867:Skin / Q000201:enzymology* / Q000473:pathology*; D013481:Superoxides / Q000378:metabolism; D014021:Tissue Preservation; D055815:Young Adult
chemical_list: D017127:Glycation End Products, Advanced; D008543:Melanins; C030524:fluorescent age pigment; D013481:Superoxides; D003094:Collagen; D045304:Cytochromes c; D004549:Elastin; D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase