Chenitar · Impact of chemical form of nickel ions on its molecular targets in some human cells
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-07-01 → 2017-06-30
- EU contribution
- €173,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Impact of chemical form of nickel ions on its molecular targets in some human cells
Nickel is classified under Regulation (EC) No. 1272/2008 as carcinogenic category 2. Besides, nickel allergy is very common worldwide, being the most common cause of contact dermatitis of the skin. Even though nickel allergy and nickel carcinogenicity are well-known health effects related to human exposure to nickel (either during production of nickel-containing products or by direct contact with the final item), the responsible molecular mechanisms events are still unknown, and require additional research. Information about the uptake of nickel to the cell and on the molecular targets of nickel is critical to resolve these health issues related to nickel. In fact, the molecular targets which determine carcinogenicity are important issues to EU according to the Scientific Committee of the European Commission. In this context, the main goal of this study is the identification of the molecular targets of different chemical forms of nickel in human skin cells as well to establish correlation between the toxicity and uptake with time of exposure, concentration and chemical form of nickel. Conclusions of the action Oxidic nickel (NiO) was found to be the most toxic nickel form towards human keratynocites among the different chemical forms of nickel tested. The determination of the nickel uptake by cells showed that the highest amount of nickel was taken up by cells treated with NiO. However, a direct relation between toxicity, chemical form and uptake by cells could not be obtained. By using a non-denaturing separation strategy, a nickel-binding protein produced by cells under stress in the presence of nickel was detected in cytosols from cells treated with different chemical forms of nickel. Finally, the development of analytical technique based on separation techniques and high-resolution electrospray mass spectrometry allowed the identification of the nickel-binding protein involved in nickel toxicity: tumor protein p63-regulated gene 1.
Data: CORDIS, © European Union
Project objective
An ambitious and multidisciplinary project is proposed to identify on the large scale the molecular targets of different chemical forms of nickel in some human cells. For this aim, a comprehensive and multidisciplinary program is proposed, including toxicity assays, non-denaturing procedures and the development of analytical schemes based on multidimensional electrophoresis and chromatographic separation.Despite nickel is classified as carcinogenic and nickel allergy is common worldwide, the molecular mechanisms responsible of nickel toxicity are not know. In this sense, to determine the carcinogenicity potential of nickel compounds, the information about the molecular targets of nickel is critical. There is an urgent need to obtain information about the molecular target depending on the chemical form of nickel, as they are not known yet. This project will study a broad range of different chemical forms of nickel in two selected human cells. Cells will be incubated with the different chemical forms in different conditions and the cytotoxicity will be measured. In order to isolate the native nickel complexes, an optimal non-denaturing procedure of will be developed. Information about the uptake of nickel to cells will be obtained and correlated with the citotoxicity results. Lastly, the identification of the molecular targets will be carried out through the development of novel analytical strategies based on the combination of different separation techniques with different detection techniques. The great novelty of this project is based on the combination of the information obatined about nickel toxicity and nickel uptake with molecular nickel speciation. The information obtained in the project will help to future understanding of molecular mechanisms of nickel related to nickel allergy and nickel carcenogicity. Additionally, the understanding of these molecular mechanisms will also help to the understanding on the mechanisms of other metal allergies.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union