ArticleMetallomics : integrated biometal science2014
Selectivity and specificity of small molecule fluorescent dyes/probes used for the detection of Zn2+ and Ca2+ in cells.
Article in Metallomics : integrated biometal science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
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- Reversible fluorescent solid porous films for detection of zinc ions in biological media.Journal of biological engineering · 2025Article
- Ratiometric Detection of ZnChemistry (Basel, Switzerland) · 2023Article
- The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart.The Journal of general physiology · 2023Review
- Intracellular Zinc Trafficking duringInternational journal of molecular sciences · 2023Article
- Human Epidermal Zinc Concentrations after Topical Application of ZnO Nanoparticles in Sunscreens.International journal of molecular sciences · 2021Article
- Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle.Nature communications · 2021Article
- Quantification of zinc intoxication ofSTAR protocols · 2021Article
- Type I Interferons Ameliorate Zinc Intoxication of Candida glabrata by Macrophages and Promote Fungal Immune Evasion.iScience · 2020Article
- Peroxiredoxin 5 deficiency exacerbates iron overload-induced neuronal death via ER-mediated mitochondrial fission in mouse hippocampus.Cell death & disease · 2020Article
- In Vitro and in Cellulo Sensing of Transition Metals Using Time-Resolved Fluorescence Spectroscopy and Microscopy.Journal of fluorescence · 2019Article
- Review
- Zinc Modulates Endotoxin-Induced Human Macrophage Inflammation through ZIP8 Induction and C/EBPβ Inhibition.PloS one · 2017Article
- Differential Effects of Iron, Zinc, and Copper onFrontiers in cellular and infection microbiology · 2017Article
- IL-4 Induces Metallothionein 3- and SLC30A4-Dependent Increase in Intracellular Zn(2+) that Promotes Pathogen Persistence in Macrophages.Cell reports · 2016Article
- Labile Low-Molecular-Mass Metal Complexes in Mitochondria: Trials and Tribulations of a Burgeoning Field.Biochemistry · 2016Review
- Newport Green, a fluorescent sensor of weakly bound cellular Zn(2+): competition with proteome for Zn(2).Metallomics : integrated biometal science · 2016Article
- Zinc transporters and zinc signaling: new insights into their role in type 2 diabetes.International journal of endocrinology · 2015Review
- Impact of Cadmium on Intracellular Zinc Levels in HepG2 Cells: Quantitative Evaluations and Molecular Effects.BioMed research international · 2015Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Fluorescent dyes are widely used in the detection of labile (free or exchangeable) Zn(2+) and Ca(2+) in living cells. However, their specificity over other cations and selectivity for detection of labile vs. protein-bound metal in cells remains unclear. We characterized these important properties for commonly used Zn(2+) and Ca(2+) dyes in a cellular environment. By tracing the fluorescence emission signal along with UV-Vis and size exclusion chromatography-inductively coupled plasma mass spectrometry (SEC-ICP-MS) in tandem, we demonstrated that among the dyes used for Zn(2+), Zinpyr-1 fluoresces in the low molecular mass (LMM) region containing labile Zn(2+), but also fluoresces in different molecular mass regions where zinc ion is detected. However, FluoZin™-3 AM, Newport Green™ DCF and Zinquin ethyl ester display weak fluorescence, lack of metal specificity and respond strongly in the high molecular mass (HMM) region. Four Ca(2+) dyes were studied in an unperturbed cellular environment, and two of these were tested for binding behavior under an intracellular Ca(2+) release stimulus. A majority of Ca(2+) was in the labile form as tested by SEC-ICP-MS, but the fluorescence from Calcium Green-1™ AM, Oregon Green® 488 BAPTA-1, Fura red™ AM and Fluo-4 NW dyes in cells did not correspond to free Ca(2+) detection. Instead, the dyes showed non-specific fluorescence in the mid- and high-molecular mass regions containing Zn, Fe and Cu. Proteomic analysis of one of the commonly seen fluorescing regions showed the possibility for some dyes to recognize Zn and Cu bound to metallothionein 2. These studies indicate that Zn(2+) and Ca(2+) binding dyes manifest fluorescence responses that are not unique to recognition of labile metals and bind other metals, leading to suboptimal specificity and selectivity.
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