Mercury-induced aggregation of human lens γ-crystallins reveals a potential role in cataract disease

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
José Antonio Domínguez-CalvaLiliana Quintanar

Abstract

Cataract disease results from non-amyloid aggregation of eye lens proteins and is the leading cause of blindness in the world. A variety of studies have implicated both essential and xenobiotic metals as potential etiological agents in cataract disease. Essential metal ions, such as copper and zinc, are known to induce the aggregation in vitro of human γD crystallin, one of the more abundant γ-crystallins in the core of the lens. In this study, we expand the investigation of metal-crystallin interactions to heavy metal ions, such as divalent lead, cadmium and mercury. The impact of these metal ions in the non-amyloid aggregation, protein folding and thermal stability of three homologous human lens γ-crystallins has been evaluated using turbidity assays, electron microscopy, electronic absorption and circular dichroism spectroscopies. Our results show that Hg(II) ions can induce the non-amyloid aggregation of human γC and γS crystallins, but not γD crystallin. The mechanism of Hg-induced aggregation involves direct metal-protein interactions, loss of thermal stability, partial unfolding of the N-terminal domain of these proteins, and formation of disulfide-bridged dimers. Putative Hg(II) binding sites in γ-crystallins involved i...Continue Reading

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Citations

Feb 11, 2020·Frontiers in Neuroscience·Eliza Maria da Costa Brito LacerdaDora Fix Ventura
Oct 6, 2018·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Lawrence Que
Feb 12, 2021·Chembiochem : a European Journal of Chemical Biology·Megan A RochaRachel W Martin
Feb 6, 2021·Biophysical Journal·Kevin PounotGiorgio Schirò
Aug 2, 2021·Experimental Eye Research·Eugene SerebryanyLiliana Quintanar
Aug 2, 2021·International Journal of Biological Macromolecules·Chandrika MittalJay Kant Yadav
Aug 3, 2021·Experimental Eye Research·Tayler F L WishartFrank J Lovicu
Apr 10, 2020·Accounts of Chemical Research·Kyle W RoskampRachel W Martin
Oct 28, 2019·Biochemistry·Kyle W RoskampRachel W Martin

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Methods Mentioned

BETA
light-scattering
size exclusion chromatography
electron microscopy
circular dichroism
protein folding

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