Journal Article

Sense in Pb<sup>2+</sup> Sensing

Henk P. M. Vijverberg and Remco H. S. Westerink

in Toxicological Sciences

Volume 130, issue 1, pages 1-3
Published in print November 2012 | ISSN: 1096-6080
Published online July 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs221
Sense in Pb2+ Sensing

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It is generally acknowledged that Pb2+, which is sequestered by live cells from their direct environment, affects a large number of cellular processes at picomolar to micromolar concentrations. However, resolving the specific molecular targets and mechanisms responsible for the neurotoxic effects of this xenobiotic metal is hampered by the lack of suitable tools to investigate the intracellular dynamics of Pb2+ at low concentrations. Fluorescent Ca2+ indicators have been used as Pb2+ sensors and have proven useful to detect cellular Pb2+ entry and to estimate the overall intracellular free Pb2+ concentration associated with adverse cellular effects. Despite the high affinity of these Ca2+ indicators for Pb2+, their utility for more advanced studies is limited. This is merely due to their moderate metal selectivity and uncertainties about the subcellular (co)localization of the indicators and the targets. Novel Pb2+ sensors, specifically developed for this purpose, still lack affinity to sense toxicologically relevant intracellular concentrations of Pb2+. Nonetheless, the development of genetically encoded protein sensors for Ca2+, Zn2+, and, recently, also for Pb2+ opens a new and promising perspective to resolve spatiotemporal changes in intracellular Pb2+ in relation to cellular signaling and intracell ular divalent metal homeostasis. Such a development is required for enabling more systematic studies of the intracellular dynamics of Pb2+, which are essential for progress in mechanistic knowledge and will ultimately reveal the critical toxic targets of Pb2+ at the subcellular and molecular level.

Keywords: Pb2#x002B;toxicity; Live-cell fluorescent imaging; Ca2#x002B;imaging; indo-1; fura-2; Met-lead 1.59; Fluorescence Resonance Energy Transfer (FRET); Metal neurotoxicity

Journal Article.  2247 words. 

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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