title: Interaction of insulin with methyl tert-butyl ether promotes molten globule-like state and production of reactive oxygen species.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Valipour
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Maghami
authors.affiliation: School of Biology, University of Tehran, Tehran, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Habibi-Rezaei
authors.affiliation: Office of Health, Safety and Environment (HSE) Oil Ministry, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Sadeghpour
authors.affiliation: Office of Health, Safety and Environment (HSE) Oil Ministry, Bandar Mahshahr, Iran.
authors.forename: Mohamad Ali
authors.initials: MA
authors.lastname: Khademian
authors.affiliation: Office of Health, Safety and Environment (HSE) Oil Ministry, Bandar Mahshahr, Iran.
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Mosavi
authors.affiliation: Departments of Ophthalmology and Visual Sciences and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran. Electronic address: moosavi@ut.ac.ir.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Moosavi-Movahedi
mesh_terms: D057446:Hydrodynamics; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism; D008738:Methyl Ethers / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000737:chemistry* / Q000378:metabolism; D014783:Viscosity
chemical_list: D007328:Insulin; D008738:Methyl Ethers; D017382:Reactive Oxygen Species; C043243:methyl tert-butyl ether
keywords: Differential scanning calorimetry; Hydrophobic patches; Insulin; Methyl tert-butyl ether; Molten globule state; Reactive oxygen species