Purchase this article with an account.
devi kalyan karumanchi, Elizabeth Gaillard, James Dillon; KINETICS OF DIABETES RELATED MODIFICATIONS IN HEAT SHOCK PROTEINS. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5742.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate the glycolytic modifications of heat shock proteins using alpha crystallin, a lens protein, as the model. This study will help us to understand the relation between ocular pathology and hyperglycemic environment.
Alpha crystallin was incubated with open chain sugars and dicarbonyl reactive intermediates at 25oC for 0.5-72 hrs. UV-vis, fluorescence, circular dichroism, light scattering and microscopy imaging techniques were performed to study the changes that occur in the structure of the protein as well as the whole lens.
The hydrodynamic diameter of α-crystallin (~18 nm) was found to increase rapidly on reaction with glycating agents. Non-tryptophan fluorescence (emission at 400-500 nm) intensity was found to increase while the surface hydrophobicity decreased over the time period. Circular dichroism data shows a significant loss of β-sheets to form random coils. SDS-PAGE and microscopic techniques confirm the formation of protein cross-links. Overall, methyl glyoxal, glyoxal and glycoaldehyde showed faster reaction kinetics compared to glucose and sucrose.
The model system can be used to explain the effect of the Maillard reaction on the heat shock proteins in diabetic patients. These modifications in vivo lead to amyloid fibril like protein deposits. The reaction kinetics involved in the glycation of heat shock proteins helps to explain the mechanism of damage in conditions like cataracts and diabetic retinopathy.
This PDF is available to Subscribers Only