Reza Yousefi
Shiraz University
Iran
Title: Modification of lens crystallins by peroxynitrite, reducing sugars and ascorbic acid; the potential implications of the basic pathomechanism underlying cataract development during ageing, eye inflammation and hyperglycemia
Biography
Biography: Reza Yousefi
Abstract
The eye lens is composed of highly stable and long-lived proteins (α, β and γ-crystallins) which perform both structural and refractive functions. Due to their limited turnover during the life span, these proteins accumulate various modifications in their structures which finally attenuate their ability in the maintenance of lens transparency. In the current study, lens crystallins were chemically modified with peroxynitrite, different types of reducing sugar and ascorbic acid, as all of these chemical agents have been already indicated to contribute in the pathogenesis of cataract development. The different spectroscopic techniques and gel mobility shift assay were applied to investigate the structural feature, stability, aggregation/oligomerization and chaperone-like activity of lens proteins after these modifications. The concentration of peroxynitrite in the lenticular tissue can be significantly elevated during inflammation and in diabetic patients. Also, chronic hyperglycemia in eye lens results in formation of advanced glycation end products (AGEs) on lens crystallins and oxidative stress. Additionally, the cupper-catalyzed oxidation of ascorbic acid to dehydroascorbate which is known as a strong modifier of lens crystallins, plays a central role in pathology of cataract diseases during aging and in patients with diabetes mellitus. In the current work, as the structural and functional impacts of these modifications were evaluated on the lens crystallins, their pathomechanisms as the causative players in development of cataract diseases during ageing, inflammation and hyperglycemia are discussed.