Involvement of different hemoprotein thiol groups of Oncorhynchus mykiss in cadmium toxicity.
Animals
Cadmium
/ chemistry
Cadmium Poisoning
Computer Simulation
Erythrocytes
Fish Proteins
/ chemistry
Hemoglobins
/ chemistry
Humans
Mitochondria
/ chemistry
Molecular Docking Simulation
Oncorhynchus mykiss
Protein Binding
Protein Conformation
Protein Multimerization
Reactive Oxygen Species
/ chemistry
Sulfhydryl Compounds
/ chemistry
Water Pollutants, Chemical
Cadmium
Haemoproteins
Metal binding sites
Molecular docking
Precipitation
Trout haemoglobin
Journal
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
ISSN: 1878-3252
Titre abrégé: J Trace Elem Med Biol
Pays: Germany
ID NLM: 9508274
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
27
07
2020
revised:
02
02
2021
accepted:
15
03
2021
pubmed:
24
3
2021
medline:
9
11
2021
entrez:
23
3
2021
Statut:
ppublish
Résumé
Cadmium is considered the seventh most toxic heavy metal as per ATSDR ranking but its mechanism of toxicity is debated. Recently, we evaluated the effects of this metal on the erythrocyte of teleost fish (Oncorhynchus mykiss) leading us to hypothesize that the pro-oxidant activity of cadmium is not linked to mitochondria but more likely to haemoglobin. In this context, the main aim of this work was to detect the ability of Cd to induce structural perturbation in haemoproteins that present different structures and thus different functional properties and to identify what sites of interaction are mainly involved. The effect of Cd on the structural destabilization of the different haemoproteins was followed spectrophometrically through their precipitation. In addition, the sites of interaction between the different haemoproteins and bivalent cadmium ions were identified by MIB server followed by molecular docking/molecular dynamics simulations both in the dimeric and tetrameric associations. Cadmium does not influence the autoxidation rate of Mb, HbA and trout HbI. However, the presence of this metal accelerates the precipitation process in trout HbIV in a dose-dependent manner. Moreover, the presence of 1-10-50-250-500-1000 μM GSH, a chelating agent, reduces the ability of cadmium to accelerate the denaturation process although it is not able to completely prevent it. In order to explain the experimental results, a computational investigations was carried out to identify the cadmium cation affinity for the studied haemoglobins and myoglobin, both in their dimeric and tetrameric forms. As a result, the highest affinity cadmium binding sites for fish HbIV are located at the interface between tetramer-tetramer association, indicating that the cation can assist supramolecular protein aggregations and induce complex precipitation. For mammalian Hb, Mb and fish HbI computational investigation did not detect any site where Cd could to induce such aggregation, in line with the experimental results. The present study provides new information on the mechanisms of toxicity of cadmium by specific interaction with trout O. mykiss haemoglobin component.
Sections du résumé
BACKGROUND
BACKGROUND
Cadmium is considered the seventh most toxic heavy metal as per ATSDR ranking but its mechanism of toxicity is debated. Recently, we evaluated the effects of this metal on the erythrocyte of teleost fish (Oncorhynchus mykiss) leading us to hypothesize that the pro-oxidant activity of cadmium is not linked to mitochondria but more likely to haemoglobin. In this context, the main aim of this work was to detect the ability of Cd to induce structural perturbation in haemoproteins that present different structures and thus different functional properties and to identify what sites of interaction are mainly involved.
METHODS
METHODS
The effect of Cd on the structural destabilization of the different haemoproteins was followed spectrophometrically through their precipitation. In addition, the sites of interaction between the different haemoproteins and bivalent cadmium ions were identified by MIB server followed by molecular docking/molecular dynamics simulations both in the dimeric and tetrameric associations.
RESULTS
RESULTS
Cadmium does not influence the autoxidation rate of Mb, HbA and trout HbI. However, the presence of this metal accelerates the precipitation process in trout HbIV in a dose-dependent manner. Moreover, the presence of 1-10-50-250-500-1000 μM GSH, a chelating agent, reduces the ability of cadmium to accelerate the denaturation process although it is not able to completely prevent it. In order to explain the experimental results, a computational investigations was carried out to identify the cadmium cation affinity for the studied haemoglobins and myoglobin, both in their dimeric and tetrameric forms. As a result, the highest affinity cadmium binding sites for fish HbIV are located at the interface between tetramer-tetramer association, indicating that the cation can assist supramolecular protein aggregations and induce complex precipitation. For mammalian Hb, Mb and fish HbI computational investigation did not detect any site where Cd could to induce such aggregation, in line with the experimental results.
CONCLUSION
CONCLUSIONS
The present study provides new information on the mechanisms of toxicity of cadmium by specific interaction with trout O. mykiss haemoglobin component.
Identifiants
pubmed: 33756184
pii: S0946-672X(21)00036-5
doi: 10.1016/j.jtemb.2021.126746
pii:
doi:
Substances chimiques
Fish Proteins
0
Hemoglobins
0
Reactive Oxygen Species
0
Sulfhydryl Compounds
0
Water Pollutants, Chemical
0
Cadmium
00BH33GNGH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
126746Informations de copyright
Copyright © 2021 Elsevier GmbH. All rights reserved.