| Autor: |
Aleo MF; Unit of Biochemistry, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, viale Europa, 11, 25123 Brescia, Italy. aleo@med.unibs.it, Morandini F, Bettoni F, Giuliani R, Rovetta F, Steimberg N, Apostoli P, Parrinello G, Mazzoleni G |
| Jazyk: |
angličtina |
| Zdroj: |
Toxicology [Toxicology] 2005 Jan 05; Vol. 206 (1), pp. 137-51. |
| DOI: |
10.1016/j.tox.2004.07.003 |
| Abstrakt: |
Tubular epithelium represents the primary target of mercuric ions (Hg(2+)) nephrotoxicity. Although widely investigated, the mechanisms of Hg(2+) cell uptake, accumulation and excretion all along the nephron remain largely unknown. In the present study, native distal tubular-derived Madin-Darby canine kidney (MDCK) cells exposed to subcytotoxic (micromolar) HgCl(2) concentrations were used for investigating specific mechanisms involved in the tubular response to toxic metals. Inductively coupled plasma-mass spectrometry (ICP-MS) was firstly used for assessing HgCl(2) solubility and then for quantifying Hg(2+) cell uptake. Exposed to HgCl(2), MDCK cells showed a rapid, but transient, Hg(2+) accumulation. The metallic cation was found to affect cell density and morphology, being these effects related to the dose and the time of exposure. In parallel, an Hg(2+)-induced up-regulation of endogenous MRP1 and MRP2 export pumps, a significant HgCl(2)-dependent induction of protective cellular thiols and an increase in the glutathione conjugates metabolism were also observed. The functional suppression of MRPs activity, obtained by MK-571 treatment, increased the Hg(2+) cell content and the sensitivity of MDCK cells to HgCl(2). Our results demonstrate that, in MDCK cells, inorganic Hg(2+) promotes the activation of specific detoxifying pathways that may, at least partly, depend on the activity of MRP transporters. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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