Статья

The effect of reactive oxygen and nitrogen species on the structure of cytoglobin: A potential tumor suppressor

Joey De BackerResearch Group PPES, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, Belgium. Electronic address: [email protected]Jamoliddin RazzokovResearch Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, BelgiumDietmar HammerschmidResearch Group PPES, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, Belgium; Biomolecular & Analytical Mass Spectrometry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, BelgiumCarl MenschResearch Group Molecular Spectroscopy, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, BelgiumZainab HafideddineResearch Group PPES, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, Belgium; The Laboratory of Biophysics and Biomedical Physics, Department of Physics, Universiteitsplein 1, Wilrijk, 1610 Antwerp, BelgiumNaresh KumarResearch Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, BelgiumGeert Van RaemdonckCenter for Proteomics, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, BelgiumMaksudbek YusupovResearch Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, BelgiumSabine Van DoorslaerChristian JohannessenResearch Group Molecular Spectroscopy, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, BelgiumFrank SobottBiomolecular & Analytical Mass Spectrometry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK; School of Molecular and Cellular Biology, University of Leeds, Leeds, UKAnnemie BogaertsResearch Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, BelgiumSylvia DewildeResearch Group PPES, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Wilrijk, 1610 Antwerp, Belgium. Electronic address: [email protected]

2018en

ABI

Аннотация

Many current anti-cancer therapies rely on increasing the intracellular reactive oxygen and nitrogen species (RONS) contents with the aim to induce irreparable damage, which subsequently results in tumor cell death. A novel tool in cancer therapy is the use of cold atmospheric plasma (CAP), which has been found to be very effective in the treatment of many different cancer cell types in vitro as well as in vivo, mainly through the vast generation of RONS. One of the key determinants of the cell's fate will be the interaction of RONS, generated by CAP, with important proteins, i.e. redox-regulatory proteins. One such protein is cytoglobin (CYGB), a recently discovered globin proposed to be involved in the protection of the cell against oxidative stress. In this study, the effect of plasma-produced RONS on CYGB was investigated through the treatment of CYGB with CAP for different treatment times. Spectroscopic analysis of CYGB showed that although chemical modifications occur, its secondary structure remains intact. Mass spectrometry experiments identified these modifications as oxidations of mainly sulfur-containing and aromatic amino acids. With longer treatment time, the treatment was also found to induce nitration of the heme. Furthermore, the two surface-exposed cysteine residues of CYGB were oxidized upon treatment, leading to the formation of intermolecular disulfide bridges, and potentially also intramolecular disulfide bridges. In addition, molecular dynamics and docking simulations confirmed, and further show, that the formation of an intramolecular disulfide bond, due to oxidative conditions, affects the CYGB 3D structure, thereby opening the access to the heme group, through gate functioning of His117. Altogether, the results obtained in this study (1) show that plasma-produced RONS can extensively oxidize proteins and (2) that the oxidation status of two redox-active cysteines lead to different conformations of CYGB.

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Идентификаторы

DOI: 10.1016/j.redox.2018.07.019

Цитирования и источники

Цитирований: 5Использованных источников: 0

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