4.7 Article

Lens Endogenous Peptide αA66-80 Generates Hydrogen Peroxide and Induces Cell Apoptosis

Journal

AGING AND DISEASE
Volume 8, Issue 1, Pages 57-70

Publisher

INT SOC AGING & DISEASE
DOI: 10.14336/AD.2016.0805

Keywords

crystallin; peptide; hydrogen peroxide; lens; cataract; amyloid

Funding

  1. National Institutes of Health [EY019878]

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In previous studies, we reported the presence of a large number of low-molecular-weight (LMW) peptides in aged and cataract human lens tissues. Among the LMW peptides, a peptide derived from alpha A-crystallin, alpha A66-80, was found in higher concentration in aged and cataract lenses. Additional characterization of the alpha A66-80 peptide showed beta sheet signature, and it formed well-defined unbranched fibrils. Further experimental data showed that alpha A66-80 peptide binds a-crystallin, impairs its chaperone function, and attracts additional crystallin proteins to the peptide a-crystallin complex, leading to the formation of larger light scattering aggregates. It is well established that A beta peptide exhibits cell toxicity by the generation of hydrogen peroxide. The alpha A66-80 peptide shares the principal properties of A beta peptide. Therefore, the present study was undertaken to determine whether the fibril-forming peptide alpha A66-80 has the ability to generate hydrogen peroxide. The results show that the alpha A66-80 peptide generates hydrogen peroxide, in the amount of 1.2 nM H2O2 per mu g of alpha A66-80 peptide by incubation at 37 degrees C for 4h. We also observed cytotoxicity and apoptotic cell death in alpha A66-80 peptide-transduced Cos7 cells. As evident, we found more TUNEL-positive cells in alpha A66-80 peptide transduced Cos7 cells than in control cells, suggesting peptide-mediated cell apoptosis. Additional immunohistochemistry analysis showed the active form of caspase-3, suggesting activation of the caspase-dependent pathway during peptide-induced cell apoptosis. These results confirm that the alpha A66-80 peptide generates hydrogen peroxide and promotes hydrogen peroxide-mediated cell apoptosis.

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