Cobalt distribution in keratinocyte cells indicates nuclear and perinuclear accumulation and interaction with magnesium and zinc homeostasis
MOULIN, C.
Laboratoire de Spéciation des Radionucléides et des Molécules [LSRM]
DAM Île-de-France [DAM/DIF]
< Leer menos
Laboratoire de Spéciation des Radionucléides et des Molécules [LSRM]
DAM Île-de-France [DAM/DIF]
Idioma
en
Article de revue
Este ítem está publicado en
Toxicology Letters. 2009, vol. 188, p. 26-32
Elsevier
Resumen en inglés
Cobalt is knownto be toxic at high concentration, to induce contact dermatosis, and occupational radiation skin damage because of its use in nuclear industry.We investigated the intracellular distribution of cobalt in ...Leer más >
Cobalt is knownto be toxic at high concentration, to induce contact dermatosis, and occupational radiation skin damage because of its use in nuclear industry.We investigated the intracellular distribution of cobalt in HaCaThumankeratinocytes as a model of skin cells, and its interaction with endogenous trace elements. Direct micro-chemical imaging based on ion beam techniques was applied to determine the quantitative distribution of cobalt in HaCaT cells. In addition, synchrotron radiation X-ray fluorescence microanalysis in tomography mode was performed, for the first time on a single cell, to determine the 3D intracellular distribution of cobalt. Results obtained with these micro-chemical techniques were compared to a more classical method based on cellular fractionation followed by inductively coupled plasma atomic emission spectrometry (ICP-AES) measurements. Cobalt was found to accumulate in the cell nucleus and in perinuclear structures indicating the possible direct interaction with genomic DNA, and nuclear proteins. The perinuclear accumulation in the cytosol suggests that cobalt could be stored in the endoplasmic reticulum or the Golgi apparatus. The multi-elemental analysis revealed that cobalt exposure significantly decreased magnesium and zinc content, with a likely competition of cobalt for magnesium and zinc binding sites in proteins. Overall, these data suggest a multiform toxicity of cobalt related to interactions with genomic DNA and nuclear proteins, and to the alteration of zinc and magnesium homeostasis.< Leer menos
Palabras clave en inglés
Toxicology
Cobalt
In vitro
Cellular chemical imaging
Trace element homeostasis
Orígen
Importado de HalCentros de investigación