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Effect of endosulfan and bisphenol A on the expression of SUMO and UBC9.

Drug and chemical toxicology (2018-11-15)
Vidhya Yarahalli Jayaram, Somesh Baggavalli, Divijendra Reddy, Srinivas Sistla, Rajyalakshmi Malempati
ABSTRACT

This study was designed to investigate possible interference of Xenobiotics with SUMOylation in eukaryotic cells. To begin with, we docked 71 chemical structures from PubChem with human SUMO1 and UBC9 protein structures using Auto Dock 4.2 and Hex 6.3 and selected five compounds for binding studies in Surface Plasmon Resonance (SPR) with human SUMO1. In SPR studies, only endosulfan showed binding to SUMO1 (Kd1.313 × 10-4 M). Further, we treated HePG2 and differentiated 3T3-L1 cells with endosulfan/bisphenol A/perfluorooctanoic acid (PFOA) to test induction of oxidative stress and SUMO isoform/UBC9 expression. Treatment with these compounds resulted in higher levels of nitric oxide (NO), NOS2A mRNA, and reactive oxygen species (ROS) associated with decreased NADPH levels. Additionally, treatment with these chemicals resulted in elevated mRNA levels of IL-6 and IL-1β in 3T3-L1 cells. In HePG2 cells, endosulfan treatment resulted in elevated mRNA levels of SUMO1, 3 and UBC9, whereas, treatment with bisphenol A resulted in increased mRNA of SUMO2, 3 and UBC9. Treatment with PFOA resulted in elevated mRNA levels of SUMO2. Apart from influencing the gene expression, endosulfan caused decrease in SUMO1-Sumoylation of few proteins. We propose that one reason for the severe health consequences of exposure to endosulfan/bisphenol could be due to induction of oxidative stress and modulation in SUMO and UBC9 gene expression.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-SUMO-1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Perfluorooctanoic acid, 95%
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose and L-glutamine, without sodium bicarbonate, powder, suitable for cell culture
Sigma-Aldrich
Pentostatin, ≥95% (HPLC)
Sigma-Aldrich
Minimum Essential Medium Eagle, With Earle′s salts, L-glutamine, and non-essential amino acids, without sodium bicarbonate, powder, suitable for cell culture