Involvement of different hemoprotein thiol groups of Oncorhynchus mykiss in cadmium toxicity |
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| Institution: | 1. Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131, Ancona, Italy;2. School of Pharmacy, University of Camerino, Camerino, MC, Italy;3. School of Pharmacy and Health Products, University of Camerino, 62032, Camerino, Italy;1. Department of Chemistry, Faculty of Science, University of Kerbala, Karbala, Iraq;2. ICP-MS Facility, Department of Chemistry, Faculty of Engineering and Physical Sciences, Guildford, Surrey, GU2 7XH, UK;1. Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 11, 1113, Sofia, Bulgaria;2. Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113, Sofia, Bulgaria;3. National and Kapodistrian University of Athens, Department of Chemistry, Laboratory of Environmental Chemistry, Panepistimiopolis, 15784, Athens, Greece;1. College of Life Sciences, Shanghai Normal University, Shanghai, 200234, China;2. Department of Obstetrics and Gynecology, Shanghai Everjoy Medical Polyclinic, 675 Minbei Road, Shanghai, 201107, China;3. Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE, 68588-0664, United States;1. Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil;2. Laboratory of Cell Culture and Cytogenetics, Environment Section, Evandro Chagas Institute, Ananindeua, PA, Brazil;3. School of Dentistry, Federal University of Pará, Belém, PA, Brazil;4. Laboratory of Toxicology, Environment Section, Evandro Chagas Institute, Ananindeua, PA, Brazil;5. Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil;1. Zoology Department, Faculty of Science, Cairo University, Egypt;2. Biology Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia;3. Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo, Egypt |
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| Abstract: | BackgroundCadmium 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.MethodsThe 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.ResultsCadmium 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.ConclusionThe present study provides new information on the mechanisms of toxicity of cadmium by specific interaction with trout O. mykiss haemoglobin component. |
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| Keywords: | Cadmium Haemoproteins Precipitation Trout haemoglobin Molecular docking Metal binding sites |
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