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Int. J. Mol. Sci. 2010, 11(11), 4556-4579; doi:10.3390/ijms11114556
Article

Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone

1
, 1,* , 1
, 2
 and 1
1 A. N. Bakh Institute of Biochemistry, Russian Academy of Sciences, Leninsky prospect 33, Moscow 119071, Russia 2 Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow 119991, Russia
* Author to whom correspondence should be addressed.
Received: 30 September 2010 / Revised: 21 October 2010 / Accepted: 9 November 2010 / Published: 15 November 2010
(This article belongs to the Section Bioinorganic Chemistry)
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Abstract

The kinetics of dithiothreitol (DTT)-induced aggregation of human recombinant insulin and the effect of α-crystallin, a representative of the family of small heat shock proteins, on the aggregation process have been studied using dynamic light scattering technique. Analysis of the distribution of the particles by size measured in the course of aggregation showed that the initial stage of the aggregation process was the stage of formation of the start aggregates with a hydrodynamic radius (Rh) of about 90 nm. When studying the effect of α-crystallin on the rate of DTT-induced aggregation of insulin, it was demonstrated that low concentrations of α-crystallin dramatically accelerated the aggregation process, whereas high concentrations of α-crystallin suppressed insulin aggregation. In the present study, at the molar stoichiometric ratio (insulin:α-crystallin) less than 1:0.5, a pronounced accelerating effect of α-crystallin was observed; whereas a ratio exceeding the value of 1:0.6 caused suppression of insulin aggregation. The mechanisms underlying the dual effect of α-crystallin have been proposed. It is assumed that heterogeneous nucleation occurring on the surface of the α-crystallin particle plays the key role in the paradoxical acceleration of insulin aggregation by α-crystallin that may provide an alternative biologically significant pathway of the aggregation process.
Keywords: aggregation; alpha-crystallin; dynamic light scattering; insulin aggregation; alpha-crystallin; dynamic light scattering; insulin
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Bumagina, Z.; Gurvits, B.; Artemova, N.; Muranov, K.; Kurganov, B. Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone. Int. J. Mol. Sci. 2010, 11, 4556-4579.

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