Protection of human γD-crystallin protein from ultraviolet C-induced aggregation by ortho-vanillin

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2021-11, Vol.261, p.120023, Article 120023
• Main Authors: Hsueh, Shu-Shun, Lu, Jian-Hong, Wu, Josephine W., Lin, Ta-Hsien, Wang, Steven S.-S.
• Format: Article
• Language: English
• Subjects: Aggregation; Cataract; Human γD-crystallin; Ortho-vanillin; Ultraviolet
• ISSN: 1386-1425
• DOI: 10.1016/j.saa.2021.120023

[Display omitted] •Ultraviolet-C (UV-C) induces human γD-crystallin (HGDC) aggregation.•Ortho-vanillin (OV) mitigates UV-C-induced HGDC aggregation.•Interactions between HGDC and OV cause structural changes in HGDC.•The results indicate that phenolic aldehyde compounds inhibit HGDC aggregation.•Insights gained herein may help with the design of novel anti-cataract agents. Cataract is known as one of the leading causes of vision impairment worldwide. While the detailed mechanism of cataratogenesis remains unclear, cataract is believed to be correlated with the aggregation and/or misfolding of human ocular lens proteins called crystallins. A 173-residue structural protein human γD-crystallin is a major γ-crystallin protein in the human eye lens and associated with the development of juvenile and mature-onset cataracts. This work is aimed at investigating the effect of a small molecule, e.g., ortho-vanillin, on human γD-crystallin aggregation upon exposure to ultraviolet-C irradiation. According to the findings of right-angle light scattering, transmission electron microscopy, and gel electrophoresis, ortho-vanillin was demonstrated to dose-dependently suppress ultraviolet-C-triggered aggregation of human γD-crystallin. Results from the synchronous fluorescence spectroscopy, tryptophan fluorescence quenching, and molecular docking studies revealed the structural change of γD-crystallin induced by the interaction/binding between ortho-vanillin and protein. We believe the outcome from this work may contribute to the development of potential therapeutics for cataract.