OCTN1 (SLC22A4) as a Target of Heavy Metals: Its Possible Role in Microplastic Threats
Microplastics represent a threat due to their ability to enter the food chain, with harmful consequences for living organisms. The riskiness of these particles is also linked to the release of other contaminants, such as heavy metals. Solute Carriers (SLCs) represent eminent examples of first-level...
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| Veröffentlicht in: | International journal of molecular sciences 2024-12, Vol.25 (23), p.13218 |
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| creator | Brunetti, Luana S Scalise, Mariafrancesca Scanga, Raffaella Console, Lara Galluccio, Michele La Russa, Mauro F Pochini, Lorena Indiveri, Cesare |
| description | Microplastics represent a threat due to their ability to enter the food chain, with harmful consequences for living organisms. The riskiness of these particles is also linked to the release of other contaminants, such as heavy metals. Solute Carriers (SLCs) represent eminent examples of first-level targets of heavy metals due to their localization on the cell surface. Putative targets of heavy metals are the organic cation transporters that form a sub-clade of the SLC22 family. Besides the physiological role in the absorption/release of endogenous organic cations, these transporters are crucial in drug disposition and their interaction with xenobiotics. In this work, the human SLC22A4, commonly known as OCTN1, was used as a benchmark to test interactions with heavy metals released by microplastics, exploiting the proteoliposome tool. The potency of metals to interfere with the OCTN1 function has been evaluated by measuring IC50 values calculated in the micromolar range. The molecular mechanism of interaction has been defined using site-directed mutagenesis and computational analyses. Finally, some chemical and physiological thiol-reacting compounds show the capacity to rescue the metal-inhibited OCTN1 function. The conclusions drawn on OCTN1 can be extended to other members of the SLC22 family and orthologous transporters in fish. |
| doi_str_mv | 10.3390/ijms252313218 |
| format | Article |
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The riskiness of these particles is also linked to the release of other contaminants, such as heavy metals. Solute Carriers (SLCs) represent eminent examples of first-level targets of heavy metals due to their localization on the cell surface. Putative targets of heavy metals are the organic cation transporters that form a sub-clade of the SLC22 family. Besides the physiological role in the absorption/release of endogenous organic cations, these transporters are crucial in drug disposition and their interaction with xenobiotics. In this work, the human SLC22A4, commonly known as OCTN1, was used as a benchmark to test interactions with heavy metals released by microplastics, exploiting the proteoliposome tool. The potency of metals to interfere with the OCTN1 function has been evaluated by measuring IC50 values calculated in the micromolar range. The molecular mechanism of interaction has been defined using site-directed mutagenesis and computational analyses. Finally, some chemical and physiological thiol-reacting compounds show the capacity to rescue the metal-inhibited OCTN1 function. 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| subjects | Animals Ethylenediaminetetraacetic acid Food chains Heavy metals Humans Metals, Heavy - metabolism Metals, Heavy - toxicity Microplastics - toxicity Organic Cation Transport Proteins - genetics Organic Cation Transport Proteins - metabolism Organisms Physiological aspects Plastic pollution Proteins Symporters - genetics Symporters - metabolism Thiols Tissues |
| title | OCTN1 (SLC22A4) as a Target of Heavy Metals: Its Possible Role in Microplastic Threats |
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