title: Photosensitized reactions mediated by the major chromophore arising from glucose decomposition, result in oxidation and cross-linking of lens proteins and activation of the proteasome.
abstract: Glucose solutions incubated at low oxygen concentration gave rise to the appearance of an absorption band in the UVA-visible region after 10 days. Further characterization evidenced that this band was composed by a single chomophore with maximum absorption bands at 335 and 365 nm. HPLC/MS and UV spectroscopy assays indicated that this product is composed by five unities of furan. Importantly, the presence of a compound with identical spectral and chromatographic properties was observed in the water-soluble fraction of cataractous human eye lenses. The photo-biological effects of this glucose-derived chromophore (GDC) have been addressed using targets of biological relevance, such as water-soluble proteins from eye lens and the proteasome present in this protein mixture. Increased protein oxidation and protein crosslinking was observed when lens proteins were exposed to UVA-visible light in the presence of GDC under a 5% and 20% oxygen atmosphere. In addition, an increased proteasome peptidase activity was also observed. However, the use of D(2)O resulted in decreased proteasome activity, suggesting that singlet oxygen promotes the impairment of proteasome activity. Our results suggest that the species generated by Type I and Type II mechanisms have opposite effects on proteasome activity, being Type I a positive activator while Type II lead to impairment of proteasome function.
authors.affiliation: Centro de Nutrición Molecular y Enfermedades Crónicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Avila
authors.forename: Sebastian
authors.initials: S
authors.lastname: Trejo
authors.forename: Martin A
authors.initials: MA
authors.lastname: Baraibar
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.forename: Eduardo
authors.initials: E
authors.lastname: Silva
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D003459:Crystallins; D046988:Proteasome Endopeptidase Complex; D005947:Glucose