Interaction of insulin with methyl tert-butyl ether promotes molten globule-like state and production of reactive oxygen species.

PubMed ID: 26193678

Author(s): Valipour M, Maghami P, Habibi-Rezaei M, Sadeghpour M, Khademian MA, Mosavi K, Sheibani N, Moosavi-Movahedi AA. Interaction of insulin with methyl tert-butyl ether promotes molten globule-like state and production of reactive oxygen species. Int J Biol Macromol. 2015 Sep;80:610-4. doi: 10.1016/j.ijbiomac.2015.07.030. Epub 2015 Jul 17. PMID 26193678

Journal: International Journal Of Biological Macromolecules, Volume 80, Sep 2015

Interaction of methyl tert-butyl ether (MTBE) with proteins is a new look at its potential adverse biological effects. When MTBE is released to the environment it enters the blood stream through inhalation, and could affect the properties of various proteins. Here we investigated the interaction of MTBE with insulin and its effect on insulin structural changes. Our results showed that insulin formed a molten globule (MG)-like structure in the presence of 8 μM MTBE under physiological pH. The insulin structural changes were studied using spectroscopy methods, viscosity calculation, dynamic light scattering and differential scanning calorimetry. To delineate the mechanisms involved in MTBE-protein interactions, the formation of reactive oxygen specious (ROS) and formation of protein aggregates were measured. The chemiluminscence experiments revealed an increase in ROS production in the presence of MTBE especially in the MG-like state. These results were further confirmed by the aggregation tests, which indicated more aggregation of insulin at 40 μM MTBE compared with 8 μM. Thus, the formation of initial aggregates and exposure of the hydrophobic patches upon formation of the MG-like state in the presence of MTBE drives protein oxidation and ROS generation.