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Bioactive copper(II) agents and their potential involvement in the treatment of copper deficiency-related orphan diseases.
Perez, Mariela Gomez; Suarez, Narjara Gonzalez; Annabi, Borhane; Mateescu, Mircea Alexandru.
Afiliación
  • Perez MG; Department of Chemistry and Center CERMO-FC, Université du Québec à Montréal, C.P. 8888, Montréal, Québec H3C 3P8, Canada. Electronic address: gomez_perez.mariela@courrier.uqam.ca.
  • Suarez NG; Department of Chemistry and Center CERMO-FC, Université du Québec à Montréal, C.P. 8888, Montréal, Québec H3C 3P8, Canada. Electronic address: gonzalez_suarez.narjara@courrier.uqam.ca.
  • Annabi B; Department of Chemistry and Center CERMO-FC, Université du Québec à Montréal, C.P. 8888, Montréal, Québec H3C 3P8, Canada. Electronic address: annabi.borhane@uqam.ca.
  • Mateescu MA; Department of Chemistry and Center CERMO-FC, Université du Québec à Montréal, C.P. 8888, Montréal, Québec H3C 3P8, Canada. Electronic address: mateescu.m-alexandru@uqam.ca.
J Inorg Biochem ; 247: 112334, 2023 10.
Article en En | MEDLINE | ID: mdl-37499466
The deregulation of copper homoeostasis can promote various diseases such as Menkes disease or hypertrophic cardioencephalomyopathy. We have recently synthesized solid copper(II) complexes ([Cu(His)2Cl2] and [Cu(Ser)2]), stable in physiological media and with potential as therapeutic agents. This report describes: i) the biocompatibility of these complexes at concentrations up to 100 µM using a differentiated Caco-2 cells model; ii) their transport across the intestinal epithelium using a transepithelial resistance assay and monitoring the amount of copper complexes at the apical and basolateral sides of the cells. The results suggest that the flow occurs through paracellular routes. The intracellular copper retention was <2.7% with no significant differences in intracellular copper content between 6 h and 48 h, suggesting an early copper retention process. Furthermore, this is the first evidence that demonstrates [Cu(His)2Cl2] and [Cu(Ser)2] induce transcriptional downregulation of the four major copper transporters (CTR1, DMT1, ATP7A, ATP7B), and the upregulation of the metallothionein gene expression. A remarkable finding was the increase in cytochrome c oxidase activity observed after the treatment of differentiated Caco-2 cells with copper(II) complexes at concentrations of 50-100 µM. The understanding of the transport mechanisms of these copper(II) complexes across the intestinal epithelium and of their subsequent biological activities could contribute to the development of optimal pharmaceutical formulations for the therapy of copper deficiency-related diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cobre / Proteínas de Transporte de Catión Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cobre / Proteínas de Transporte de Catión Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos