Advances in the role of HCV nonstructural protein 5a (NS5A) of 3a genotype in inducing insulin resistance by possible phosphorylation of AKT/PKB.

Authors:
Shazia Rafique
Shazia Rafique
University of the Punjab
Lahore | Pakistan
Sadia Zahid
Sadia Zahid
National Center of Excellence in Molecular Biology
Lahore | Pakistan
Mobeen Munir
Mobeen Munir
University of Education Lahore
Muhammad Idrees
Muhammad Idrees
University of the Punjab
Lahore | Pakistan
Muhammad Ilyas
Muhammad Ilyas
COMSATS Institute of Information Technology
Islamabad | Pakistan
Tayyab Husnain
Tayyab Husnain
University of the Punjab
Pakistan

Sci Rep 2019 Apr 16;9(1):6150. Epub 2019 Apr 16.

Centre of Excellence in Molecular Biology, University of Punjab, Lahore, 54000, Lahore, Pakistan.

HCV genes interfere with host cellular genes and play crucial role in pathogenesis. The mechanism under which HCV genes induce insulin resistance is not much clear. This study is aimed to examine the role of HCV NS5A in inducing insulin resistance by examining its affect in the phosphorylation level of AKT/PKB. In the present study, HepG2 cells were transfected with HCV NS5A and after 24 hours of transfection, protein was extracted from cells that were pre induced with insulin at three different time intervals i.e. 1hour, 2 hours and 3hours. Dot Blot analysis was performed to study the phosphorylation level of AKT. Results showed that there is clear upregulation of serine 473 phosphorylation level of AKT in NS5A transfected cells as compared with control (without NS5A). In conclusion, upregulation of serine 473 phosphorylation by NS5A of HCV genotype 3a suggests that this gene impairs the normal insulin AKT/PKB signaling pathway that leads towards insulin resistance and Type 2 diabetes mellitus. Therefore, HCV non-structural protein NS5A should be considered as promising candidate to be studied in detail for HCV induced insulin resistance and should be regarded as a therapeutically important target for the prevention of chronic liver diseases.

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Source
http://www.nature.com/articles/s41598-019-42602-2
Publisher Site
http://dx.doi.org/10.1038/s41598-019-42602-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468007PMC
April 2019
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