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

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• 作者：Felipe Á ; vila^a ; Sebastian Trejo^c ; Martin A. Baraibar^b ; Bertrand Friguet^b ; Eduardo Silva^c ; ^{esilva@puc.cl}
• 关键词：Cataract ; Glucose degradation products ; Photosensitization ; Protein crosslinking ; Proteasome ; Aging
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2012
• 期刊代码：19_09254439
• 类别：bio
• 出版时间：April, 2012
• 卷：1822
• 期：4
• 页码：564-572
• 文件大小：917 K

摘要

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 D₂O 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.