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Life Sci. 2012 Dec 10;91(23-24):1216-20. doi: 10.1016/j.lfs.2012.09.014. Epub 2012 Oct 5.

Clioquinol-induced increase and decrease in the intracellular Zn2+ level in rat thymocytes.

Author information

1
Laboratory of Cellular Signaling, Division of Environmental Symbiosis Studies, Graduate School of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.

Abstract

AIMS:

Clioquinol is emerging as a potential therapy for some diseases, such as Alzheimer disease and cancer. This agent is a lipophilic chelator of Zn(2+). In this study, the effect of clioquinol on the intracellular Zn(2+) level was examined in order to gain insights into the toxicological profile of clioquinol.

MAIN METHODS:

The effect of clioquinol was estimated using a flow cytometer and FluoZin-3, a fluorescent indicator for Zn(2+), in rat thymocytes.

KEY FINDINGS:

Clioquinol, at concentrations ranging from 10 to 300 nM, augmented FluoZin-3 fluorescence in a concentration-dependent manner. However, the effect induced by 1 μM clioquinol was less than that by 300 nM clioquinol. Removal of extracellular Zn(2+), using the membrane impermeable Zn(2+)-chelator diethylenetriamine-N,N,N',N″,N″-pentaacetic acid (DTPA), abolished the clioquinol-induced augmentation of FluoZin-3 fluorescence. Clioquinol did not augment Fluo-3 fluorescence, an indicator of intracellular Ca(2+), in the presence of DTPA. The results suggested that clioquinol caused an extracellular Zn(2+)-dependent increase in the intracellular Zn(2+) concentration. However, in the presence of DTPA, clioquinol at micromolar concentrations (1-10 μM) attenuated FluoZin-3 fluorescence in a concentration-dependent manner. Clioquinol even at 10 μM did not affect FluoZin-3 fluorescence under cell-free condition. The concentration-response relationship for the clioquinol induced change in Zn(2+) level appeared to be bell-shaped. These results indicate that micromolar concentrations of clioquinol, without chelated Zn(2+), decrease intracellular Zn(2+) concentration.

SIGNIFICANCE:

The effect of clioquinol on the intracellular Zn(2+) level varies, depending on the extracellular Zn(2+) concentration and the clioquinol concentration. Clioquinol may therefore exert various types of Zn(2+)-dependent cytotoxicity.

PMID:
23044228
DOI:
10.1016/j.lfs.2012.09.014
[Indexed for MEDLINE]

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