Fluorescent Sensors for Measuring Metal Ions in Living Systems

Carter, Kyle P.; Young, Alexandra M.; Palmer, Amy E.

doi:10.1021/cr400546e

Cited by 2,133 publications

(1,235 citation statements)

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“…Two main families of FRET-based Zn 2+ sensors have been developed, namely the Zap-sensors by the Palmer group [51], and the eCALWYsensors by the Merkx group and ourselves [52]. Free cytosolic zinc concentrations measured using these FRET-sensors were approximately in the same range as those measured with chemical probes or hybrid sensors, and it is generally agreed now that free zinc is around a few hundreds of picomolar [53][54][55]. Both FRET sensor families have been targeted to intracellular organelles such as the ER, the nucleus, the mitochondria or the Golgi apparatus by in-frame fusion with suitable targeting motifs [51,[56][57][58].…”

Section: Free Zn 2+ Concentrations In the β Cellmentioning

confidence: 99%

Zinc and diabetes

Chabosseau

Rutter

2016

Archives of Biochemistry and Biophysics

149

104

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Zn 2+ ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet β and α cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn 2+ ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions. Abbreviation ISG: Insulin Secreting Granules; T2D: Type 2 Diabetes; T1D: Type 1 Diabetes; 2 Diabetes mellitus is a common metabolic disease, affecting approximately 9% of the adult population worldwide. It is characterized by high circulating glucose levels over a prolonged period of time which leads to long-term health complications [1]. Type 1 Diabetes (T1D) involves the autoimmune destruction of insulin-secreting β cells while Type 2 Diabetes (T2D) is linked to both a decrease of insulin release and deficient hormone action on targeted organs [2].The links among Zn 2+ , diabetes and insulin were established in the 1930s, a decade after the discovery of the hormone, when a study showed crystallized insulin contains Zn 2+ and that Zn 2+ , along with other metal ions, could reversibly trigger insulin crystallization [3]. Zinc was later demonstrated to prolong insulin action when co-injected with the hormone [4].These early studies, as well as much more recent findings showing association between T2D risk and the inheritance of gene variants encoding a critical β cell Zn 2+ transporter, ZnT8[5] have generated considerable interest in the role of Zn 2+ in diabetes aetiology and as a possible therapeutic target [6]. Zinc and the diabetic patientScott and Fisher were the first to report a direct link between zinc and diabetes in patients.While assessing the insulin content in the pancreas of diabetic patients compared to nondiabetic cadavers, they showed that in the former group zinc content was reduced by 75 % [7].Epidemiological studies also demonstrated that diabetes and whole body zinc status are associated [8][9][10][11]. In T1D and T2D patients, serum zinc levels are significantly decreased [9][10][11], this being associated with an increased zinc urinary loss [8].Zinc may have important anti-oxidant properties, as it acts as a cofactor of the superoxide dismutase enzyme which regulates the detoxification of reactive oxygen species, regulating the expression and protecting against the oxidative stress induced by chronic hyperglycaemia (for review, [12]). Furthermore, zinc inhibits alpha-ketoglutarate-dependent mitochondrial respiration suggesting that Zn 2+ can interfere with mitochondrial antioxidant production and may also stimulate production of reactive oxygen [13].Zinc supplementation h...

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Section: Free Zn 2+ Concentrations In the β Cellmentioning

confidence: 99%

Zinc and diabetes

Chabosseau

Rutter

2016

Archives of Biochemistry and Biophysics

149

104

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“…In contrast, the unsubstituted cerium sandwich complex, CePc 2 , which is known to contain a tetravalent (Ce 4+ ) cation, displays no appreciable absorption intensity in the 500 nm spectral region. 34,36 On the basis of this comparison, as well as other considerations, the authors concluded that in solution the Ce 4+ oxidation state dominates for the Ce(15c5Pc) 2 complex, but upon the formation of monolayers, IET leads to the Ce 3+ oxidation state predominating.…”

Section: Intramolecular Et Systemsmentioning

confidence: 91%

“…Depending on the substitution pattern of the tetrapyrrolic ligands bound to the cerium metal, overall neutral complexes but differing in the oxidation state of cerium and hence the charge on the ligand, have been reported. 36 Selektor and coworkers studied the physicochemical properties of Langmuir-type monolayer films of Ce(15c5Pc) 2 . The absorption spectrum of the Ce(15c5Pc) 2 film (recorded by differentialreflection absorption spectrometry) was substantially different from that of the chloroform solution from which it was cast (Fig.…”

Section: Intramolecular Et Systemsmentioning

confidence: 99%

“…However, it was unclear whether the Pc core was oxidized by an external oxidant or as the result of internal electron transfer to the metal center (IET, i.e., Ce 4+ -Ce 3+ ). To clarify which pathway led to the observed oxidation, monolayers of various other double-decker lanthanide complexes (Ln(15c5Pc) 2 where Ln = Pr 3+ , Tb 3+ , Yb 3+ , and Lu 3+ ) were prepared and investigated. In contrast to what was seen with cerium, in the case of the control lanthanide(III) films, the absorption spectra of the monolayers closely matched their respective solution state spectra.…”

Section: Intramolecular Et Systemsmentioning

confidence: 99%

“…Interestingly, compression of Ce(15c5Pc) 2 monolayers results in the reformation of the Ce 4+ oxidation state. Above 27 mN m À1 pressure, the absorption spectra of Ce(15c5Pc) 2 monolayers reverts to a pattern similar to that of the solution-state spectra (Fig.…”

Section: View Article Onlinementioning

confidence: 99%

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Supramolecular electron transfer-based switching involving pyrrolic macrocycles. A new approach to sensor development?

et al. 2015

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This Feature focuses on pyrrolic macrocycles that can serve as switches via energy-or electron transfer (ET) mechanisms. Macrocycles operating by both ground state (thermodynamic) and photoinduced ET pathways are reviewed and their ability to serve as the readout motif for molecular sensors is discussed.The aim of this article is to highlight the potential utility of ET in the design of systems that perform molecular switching or logic functions and their applicability in chemical sensor development. The conceptual benefits of this paradigm are illustrated with examples drawn mostly from the authors' laboratories.

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Mobile zinc as a modulator of sensory perception

Goldberg

Lippard

2022

FEBS Letters

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Mobile zinc is an abundant transition metal ion in the central nervous system, with pools of divalent zinc accumulating in regions of the brain engaged in sensory perception and memory formation. Here, we present essential tools that we developed to interrogate the role(s) of mobile zinc in these processes. Most important are (a) fluorescent sensors that report the presence of mobile zinc and (b) fast, Zn‐selective chelating agents for measuring zinc flux in animal tissue and live animals. The results of our studies, conducted in collaboration with neuroscientist experts, are presented for sensory organs involved in hearing, smell, vision, and learning and memory. A general principle emerging from these studies is that the function of mobile zinc in all cases appears to be downregulation of the amplitude of the response following overstimulation of the respective sensory organs. Possible consequences affecting human behavior are presented for future investigations in collaboration with interested behavioral scientists.

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Fluorescent Sensors for Measuring Metal Ions in Living Systems

Cited by 2,133 publications

References 340 publications

Zinc and diabetes

Zinc and diabetes

Supramolecular electron transfer-based switching involving pyrrolic macrocycles. A new approach to sensor development?

Mobile zinc as a modulator of sensory perception

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