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

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 th...

Full description

Bibliographic Details
Main Authors: Boris Kurganov, Konstantin Muranov, Natalya Artemova, Bella Gurvits, Zoya Bumagina
Format: Article
Language:English
Published: MDPI AG 2010-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/11/11/4556/
_version_ 1811248512409534464
author Boris Kurganov
Konstantin Muranov
Natalya Artemova
Bella Gurvits
Zoya Bumagina
author_facet Boris Kurganov
Konstantin Muranov
Natalya Artemova
Bella Gurvits
Zoya Bumagina
author_sort Boris Kurganov
collection DOAJ
description 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.
first_indexed 2024-04-12T15:29:24Z
format Article
id doaj.art-9ae941040aba49e9888c32f05ea2a493
institution Directory Open Access Journal
issn 1422-0067
language English
last_indexed 2024-04-12T15:29:24Z
publishDate 2010-11-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-9ae941040aba49e9888c32f05ea2a4932022-12-22T03:27:09ZengMDPI AGInternational Journal of Molecular Sciences1422-00672010-11-0111114556457910.3390/ijms11114556Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a ChaperoneBoris KurganovKonstantin MuranovNatalya ArtemovaBella GurvitsZoya BumaginaThe 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.http://www.mdpi.com/1422-0067/11/11/4556/aggregationalpha-crystallindynamic light scatteringinsulin
spellingShingle Boris Kurganov
Konstantin Muranov
Natalya Artemova
Bella Gurvits
Zoya Bumagina
Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone
International Journal of Molecular Sciences
aggregation
alpha-crystallin
dynamic light scattering
insulin
title Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone
title_full Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone
title_fullStr Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone
title_full_unstemmed Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone
title_short Paradoxical Acceleration of Dithiothreitol-Induced Aggregation of Insulin in the Presence of a Chaperone
title_sort paradoxical acceleration of dithiothreitol induced aggregation of insulin in the presence of a chaperone
topic aggregation
alpha-crystallin
dynamic light scattering
insulin
url http://www.mdpi.com/1422-0067/11/11/4556/
work_keys_str_mv AT boriskurganov paradoxicalaccelerationofdithiothreitolinducedaggregationofinsulininthepresenceofachaperone
AT konstantinmuranov paradoxicalaccelerationofdithiothreitolinducedaggregationofinsulininthepresenceofachaperone
AT natalyaartemova paradoxicalaccelerationofdithiothreitolinducedaggregationofinsulininthepresenceofachaperone
AT bellagurvits paradoxicalaccelerationofdithiothreitolinducedaggregationofinsulininthepresenceofachaperone
AT zoyabumagina paradoxicalaccelerationofdithiothreitolinducedaggregationofinsulininthepresenceofachaperone