Zinc increases phorbol ester receptors in intact B‐cells, neutrophil polymorphs and platelets

Forbes, Ian J.; Zalewski, Peter D.; Hurst, N P; Giannakis, C.; Whitehouse, M. W.

doi:10.1016/0014-5793(89)81388-2

Cited by 29 publications

(21 citation statements)

References 7 publications

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“…5). Zn2+ is incorporated into synaptic terminals (35) and induces PKC translocation in several cells (36,37). Indeed, we found that addition of Zn2+ to guinea pig cerebral homogenate induced translocation of PKC in a dose-dependent manner (data not shown).…”

Section: Discussionmentioning

confidence: 74%

NMDA Induces Protein Kinase C Translocation in Guinea Pig Cerebral Synaptoneurosomes.

1991

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ABSTRACT-N-methyl-D-aspartate (NMDA)-induced translocation of protein kinase C from the cytosol to membrane fractions was examined by the [3H]phorbol 12,13 dibutyrate (PDBu) binding method in guinea pig cerebral synaptoneurosomes. Pre treatment of synaptoneurosomes with NMDA, but not that with quisqualate or kain ate, induced changes in the distribution of [3H]PDBu binding in the cytosol and mem brane fractions in a dose-dependent manner. The NMDA-induced changes of the binding were completely dependent on Ca 2+ and inhibited by NMDA receptor anta gonists Mgt+, 2-amino-5-phosphonovaleric acid and ketamine, but not by Zn2+. Glycine slightly potentiated the NMDA-induced changes of [3H]PDBu binding. NMDA stimulated Ca 2+ uptake but not the phosphoinositide hydrolysis in the synap toneurosomes. These results suggest that NMDA enhances Ca 2+ influx through receptor-operated Ca 2+ channels, increasing intracellular calcium concentration and thereby induces translocation of protein kinase C.The excitatory amino acids, L-glutamate and L-aspartate, appear to be the major ex citatory neurotransmitters in the vertebrate central nervous system (CNS) (1). It is now well-known that there are three main recep tors for excitatory amino acids, N-methyl-D aspartate (NMDA), quisqualate and kainate receptors. Of these three receptors, NMDA receptors are concerned with various brain functions such as memory and neuronal death (2-4). Long-term potentiation (LTP), a long lasting increase in the synaptic efficacy, which is evoked by a brief high-frequency stimula tion (5), plays a crucial role in learning and memory (4). LTP, which is initially observed in the hippocampus, has now been recognized in a variety of brain structures. Induction of LTP, especially in the CA1 region of the hip pocampus, requires the activation of NMDA receptors (6), and maintenance of LTP is de pendent on the activation of protein kinase C (PKC) (7,8). Activation of NMDA receptors opens the receptor-operated Ca 2+ channels and thereby elicits a sustained Ca 2+ influx. One of the cellular events observed after Ca 2+ influx is the translocation of PKC from the cytosol to membranes, which results in a sub sequent activation of the enzyme (9, 10). Vac carino et al. (11) reported that stimulation of glutamate receptors elicits a translocation of soluble PKC into the membranes of cultured cerebellar neurons. The receptor subtypes re lated to PKC translocation seem to be a NMDA-type, because the effect is Mgt+ sensitive and blocked by novel NMDA recep tor antagonists (11).

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Section: Discussionmentioning

confidence: 74%

NMDA Induces Protein Kinase C Translocation in Guinea Pig Cerebral Synaptoneurosomes.

1991

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“…We have used the zinc-ionophore, pyrithione (Pyr), which forms a 2:1 (ligand:metal) hydrophobic complex and shuttles zinc across membranes down a concentration gradient. 13 To follow the influx of zinc into cells we loaded brain slices with the acetoxymethyl (AM) ester form of the zinc-sensitive indicator FluoZin-3 14 that leads to accumulation of the probe intracellularly. Application of the membrane impermeant chelator Ca-EDTA 15 leads to a small reduction in the signal confirming that most of the signal arises from intracellularly entrapped probe (Figure 3).…”

Section: ■ Resultsmentioning

confidence: 99%

Evidence for an Extracellular Zinc-Veneer in Rodent Brains from Experiments with Zn-Ionophores and ZnT3 Knockouts

Nydegger

Rumschik

Zhao

et al. 2012

ACS Chem. Neurosci.

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Ionic zinc is found at a high concentration in some glutamatergic vesicles of the mammalian brain. Ionic zinc is also found chelated to macromolecules in the extracellular space, constituting what has been called the "zinc veneer". In this communication we show that the zinc ionophore, pyrithione, can be used to demonstrate the presence of the veneer. Application of pyrithione without added ionic zinc to rodent hippocampal slices mobilizes extracellular zinc, which can be detected intracellularly by the zinc probe FluoZin-3. In addition, we show that ZnT3 null mice, which lack the transporter responsible for stocking synaptic vesicles, nevertheless do have a zinc veneer, albeit diminished compared to wild type animals. The presence of the zinc veneer in ZnT3 null mice may account for the absence of any marked deficit in these animals. KEYWORDS: Zinc, Synaptic, Ionophore, Hippocampus W ork spanning a number of decades has shown that the synaptic vesicles in some glutamatergic terminals are stocked with zinc.1 A combination of chemical and physical techniques has been used to demonstrate that the zinc in the vesicles is in a loosely chelated form.2 This culminated in the finding that the protein ZnT3 is essential for loading zinc into the vesicles.3 Although there is some evidence that zinc may act as neuromodulator, its precise role remains obscure. 4 Free transition metal concentrations are kept very low within cells.5 This prevents the mismetalation of proteins, restricts the possibility of metals precipitating proteins and metals entering into free radical reactions. For the case of copper which is redox active, and hence needs to be kept under tight control, this is very well understood. 6 Less is known about zinc but it is becoming clear that it has a free metal concentration of about ∼0.5 nM 7 and is controlled by the interplay between zinc influx, efflux, and buffering (Figure 1).The extracellular space in the brain, which constitutes ∼20% of total volume, is an important pathway for the passage of molecules.8 It is believed that zinc is released during the course of synaptic transmission by certain glutamatergic terminals and that there is a transient elevation in the free metal concentration in the extracellular space, approaching somewhere between 1 and 300 μM.1 However, recent work from our lab has called into question whether synaptic zinc is indeed released in an unfettered form. What are the levels of zinc in quiescent periods in the extracellular space? We have found evidence for what we have termed the "zinc veneer", that is zinc loosely associated with the extracellular aspect of neurons and probably glia.10 Application of the membrane impermeant zinc-sensitive fluorescent probe FluoZin-3, led to the increase of fluorescence overlying the

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“…209 The elevation of an electron from HOMO to LUMO upon photo-excitation leads to the change of dipole moment. The DFT calculation of FMOs usually agrees with the qualitative conclusion drawn from analyzing the resonance structures, as shown in Fig.…”

Section: Singlet State Ligand-centered Photophysical Processesmentioning

confidence: 99%

“…Pyrithione is a widely used ionophore for transporting Zn(II) ions in the form of [ZnL 2 ] to intracellular space. 209,210 Hydroxamates are potent Zn(II) protease inhibitors. 211 These compounds offer two oxygen donors which are hard Lewis bases (see below) and are also good ferric ion ligands.…”

Section: Zn(ii) Coordination Chemistrymentioning

confidence: 99%

Zn(ii)-coordination modulated ligand photophysical processes – the development of fluorescent indicators for imaging biological Zn(ii) ions

et al. 2014

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Molecular photophysics and metal coordination chemistry are the two fundamental pillars that support the development of fluorescent cation indicators. In this article, we describe how Zn(II)-coordination alters various ligand-centered photophysical processes that are pertinent to developing Zn(II) indicators. The main aim is to show how small organic Zn(II) indicators work under the constraints of specific requirements, including Zn(II) detection range, photophysical requirements such as excitation energy and emission color, temporal and spatial resolutions in a heterogeneous intracellular environment, and fluorescence response selectivity between similar cations such as Zn(II) and Cd(II). In the last section, the biological questions that fluorescent Zn(II) indicators help to answer are described, which have been motivating and challenging this field of research.

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Zinc increases phorbol ester receptors in intact B‐cells, neutrophil polymorphs and platelets

Cited by 29 publications

References 7 publications

NMDA Induces Protein Kinase C Translocation in Guinea Pig Cerebral Synaptoneurosomes.

NMDA Induces Protein Kinase C Translocation in Guinea Pig Cerebral Synaptoneurosomes.

Evidence for an Extracellular Zinc-Veneer in Rodent Brains from Experiments with Zn-Ionophores and ZnT3 Knockouts

Zn(ii)-coordination modulated ligand photophysical processes – the development of fluorescent indicators for imaging biological Zn(ii) ions

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