Paradoxical acceleration of dithiothreitol-induced aggregation of insulin in the presence of a chaperone.

Paradoxical acceleration of dithiothreitol-induced aggregation of insulin in the presence of a chaperone.
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DOI:
10.3390/ijms11114556
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发表时间:
2010-11-15
影响因子:
5.6
通讯作者:
Kurganov B
Kurganov B
中科院分区:
生物学2区
文献类型:
--
作者:
Bumagina Z;Gurvits B;Artemova N;Muranov K;Kurganov B

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用动态光散射技术研究了二硫苏糖醇(DTT)诱导人重组胰岛素聚集的动力学及小分子热休克蛋白家族的代表--α-晶状体蛋白对聚集过程的影响。通过在聚集过程中测量的尺寸分析颗粒的分布表明,聚集过程的初始阶段是形成流体动力学半径(Rh)为约90 nm的起始聚集体的阶段。当研究α-晶状体蛋白对DTT诱导的胰岛素聚集速率的影响时,证明低浓度的α-晶状体蛋白显著加速聚集过程,而高浓度的α-晶状体蛋白抑制胰岛素聚集。在本研究中,在摩尔化学计量比(胰岛素:α-晶状体蛋白)小于1:0.5时,观察到α-晶状体蛋白的显著加速作用;而超过1:0.6的比值会导致胰岛素聚集的抑制。并提出了α-晶状体蛋白双重作用的机制。据推测,在α-晶状体蛋白颗粒表面上发生的异质成核在α-晶状体蛋白对胰岛素聚集的矛盾加速中起关键作用,这可能提供聚集过程的替代生物学意义途径。
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.
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