Investigation of Salbutamol effect on alpha-1 antitrypsin polymerization reduction

Hosseini, Seyedeh Maryam; Hasannia, Sadegh; Ranjbar, Bijan

Investigation of Salbutamol effect on alpha-1 antitrypsin polymerization reduction

Document Type : Original Research

Authors

Seyedeh Maryam Hosseini ¹

Sadegh Hasannia ²

Bijan Ranjbar ³

¹ Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

² Associate Professor, Biochemistry Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran

³ Professor, Biophysics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran

Abstract

Human alpha1-antitrypsin is a glycoprotein comprised of 394 amino acids and 52 kDa molecular weight, which is mostly synthesized and secreted by hepatocytes, diffuses to interstitial lung tissues, and has an essential function to protected tissues against neutrophil elastase. One of the significant challenges in dealing with alpha-1-antitrypsin is the structural instability of the folded form of protein and, consequently, the accumulation of polymers in lung tissue. This makes patients vulnerable to chronic obstructive pulmonary disease, severe asthma, and emphysema. Intravenous augmentation therapy of alpha 1-antitrypsin is one of the most prevalent therapies. Moreover, patients who are candidates for that have respiratory symptoms, and the use of bronchodilator (Salbutamol) is the first recommended standard treatment. In this study, protein purification was performed by using high-performance affinity chromatography and, its purity was confirmed by gel electrophoresis. The effect of different concentrations of salbutamol on heat-induced polymerization at 60 ° C was investigated by non-denaturing polyacrylamide gel electrophoresis, dynamic light scattering (DLS), and circular dichroism (CD) techniques. Protein activity was measured by trypsin inhibitor capacity (TIC) assay. The results indicated that salbutamol decreases the rate of polymerization by reducing the flexibility of the reactive center loop, thus decelerate protein activity reduction. Therefore, salbutamol can be an appropriate supplementary for alpha 1-antitrypsin and a proper option for the treatment of protein polymerization associated diseases.

Keywords

Alpha 1-antitrypsin

Salbutamol

polymerization

Activity

Circular Dichroism Spectroscopy

20.1001.1.23222115.1399.11.3.10.3

Subjects

Molecular biotechnology

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