Transport of Reactive Oxygen and Nitrogen Species across Aquaporin: A Molecular Level Picture.

Maksudbek Yusupov,Rodrigo M Cordeiro,Annemie Bogaerts,Jamoliddin Razzokov

doi:10.1155/2019/2930504

Abstract

Aquaporins (AQPs) are transmembrane proteins that conduct not only water molecules across the cell membrane but also other solutes, such as reactive oxygen and nitrogen species (RONS), produced (among others) by cold atmospheric plasma (CAP). These RONS may induce oxidative stress in the cell interior, which plays a role in cancer treatment. The underlying mechanisms of the transport of RONS across AQPs, however, still remain obscure. We apply molecular dynamics simulations to investigate the permeation of both hydrophilic (H2O2 and OH) and hydrophobic (NO2 and NO) RONS through AQP1. Our simulations show that these RONS can all penetrate across the pores of AQP1. The permeation free energy barrier of OH and NO is lower than that of H2O2 and NO2, indicating that these radicals may have easier access to the pore interior and interact with the amino acid residues of AQP1. We also study the effect of RONS-induced oxidation of both the phospholipids and AQP1 (i.e., sulfenylation of Cys191) on the transport of the above-mentioned RONS across AQP1. Both lipid and protein oxidation seem to slightly increase the free energy barrier for H2O2 and NO2 permeation, while for OH and NO, we do not observe a strong effect of oxidation. The simulation results help to gain insight in the underlying mechanisms of the noticeable rise of CAP-induced RONS in cancer cells, thereby improving our understanding on the role of AQPs in the selective anticancer capacity of CAP.

Highlights

In recent years, cold atmospheric plasma (CAP) application in cancer treatment has shown beneficial effects [1]
We investigate the permeation of both hydrophilic (H2O2 and OH) and hydrophobic (NO2 and NO) reactive oxygen and nitrogen species (RONS) through the AQP1 pores of the native (NAT) and oxidized (OXL and OXP) systems
The aim of our study was to better understand the permeation process of both hydrophilic (H2O2 and OH) and hydrophobic (NO2 and NO) RONS across the pores of AQP1, which is a transmembrane protein, as well as the effect of both lipid and protein oxidation, which can be induced by these RONS

Summary

Introduction

Cold atmospheric plasma (CAP) application in cancer treatment has shown beneficial effects [1]. Experiments already evidenced that CAP may selectively eliminate cancer cells, leaving homologous normal cells less damaged [2,3,4,5]. This and other features of CAP, such as causing no pain in patients, no thermal and electrical damage, and low cost [6, 7], might give an advantage to CAP over traditional anticancer therapies. It is generally believed that the selective anticancer capacity of CAP is linked to the higher levels of RONS that are generated in cancer cells, while normal cells experience a relatively modest increase (if any) in RONS levels [4, 8,9,10]. The underlying mechanisms of the distinct increase of intracellular RONS are still not fully understood, several explanations have already been proposed in the literatures [13,14,15]

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Conclusion