Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat

Frederickson, Christopher J.; Klitenick, Mark A.; Manton, W. I.; Kirkpatrick, Joel B.

doi:10.1016/0006-8993(83)90858-2

Cited by 338 publications

(149 citation statements)

References 29 publications

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“…The effective zinc concentration was 1-10 M, in the same range as that which has been shown to stimulate A␤ amyloid aggregation (45). Zinc is present at high concentrations in cerebral cortex and hippocampal formation (46), two brain regions which are particularly prone to develop the neuropathology of Alzheimer's disease. Moreover, high concentrations of zinc have been found in cycad-derived flour which has been linked to the high incidence of the amyotrophic lateral sclerosis/Parkinsonism-dementia complex on the island of Guam, a condition characterized by an extensive fibrillary tau pathology (47,48).…”

Section: Effects Of Glycosaminoglycans On Phosphorylation Of Tau Bymentioning

confidence: 92%

Alzheimer-like Changes in Microtubule-associated Protein Tau Induced by Sulfated Glycosaminoglycans

Hasegawa¹,

Crowther

Jakes

et al. 1997

Journal of Biological Chemistry

198

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Hyperphosphorylated microtubule-associated protein tau is the major proteinaceous component of the paired helical and straight filaments which constitute a defining neuropathological characteristic of Alzheimer's disease and a number of other neurodegenerative disorders. We have recently shown that full-length recombinant tau assembles into Alzheimer-like filaments upon incubation with heparin. Heparin also promotes phosphorylation of tau by a number of protein kinases, prevents tau from binding to taxol-stabilized microtubules, and produces rapid disassembly of microtubules assembled from tau and tubulin. Here, we have used the above parameters to study the interactions between tau protein and a number of naturally occurring and synthetic glycosaminoglycans. We show that the magnitude of the glycosaminoglycan effects is proportional to their degree of sulfation. Thus, the strongly sulfated glycosaminoglycans dextran sulfate, pentosan polysulfate, and heparin were the most potent, whereas the non-sulfated dextran and hyaluronic acid were without effect. The moderately sulfated glycosaminoglycans heparan sulfate, chondroitin sulfate, and dermatan sulfate had intermediate effects, whereas keratan sulfate had little or no effect. These in vitro interactions between tau protein and sulfated glycosaminoglycans reproduced the known characteristics of paired helical filament-tau from Alzheimer's disease brain. Sulfated glycosaminoglycans are present in nerve cells in Alzheimer's disease brain in the early stages of neurofibrillary degeneration, suggesting that their interactions with tau may constitute a central event in the development of the neuronal pathology of Alzheimer's disease. The paired helical filament (PHF)1 and the related straight filament (SF) are the major components of the neurofibrillary deposits that form a defining neuropathological characteristic of Alzheimer's disease and a number of other neurodegenerative disorders (reviewed in Ref. 1). They are composed of microtubule-associated protein tau, in a hyperphosphorylated state. Mass spectrometry and immunological studies have identified a large number of phosphorylation sites in PHF-tau (2-11). Some of these sites are not phosphorylated in tau from normal brain, whereas others are phosphorylated to a greater extent in PHF-tau than in tau from normal brain. Many phosphorylated sites are serine/threonine-prolines. Consequently, tau protein can be phosphorylated in vitro at many of these sites by proline-directed protein kinases, such as mitogen-activated protein (MAP) kinase (12-14), stress-activated protein (SAP) kinases (15, 16), glycogen synthase kinase-3 (GSK3) (17-19), and neuronal cdc2-like kinase (NCLK) (20, 21). Moreover, cAMP-dependent protein kinase and Ca 2ϩ /calmodulin-dependent protein kinase II phosphorylate tau at specific sites in vitro, some of which are also phosphorylated in PHF-tau (22-24). Hyperphosphorylation of tau results in its inability to bind to microtubules and is believed to precede PHF assembly (25)(26)(27). However, it ...

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Section: Effects Of Glycosaminoglycans On Phosphorylation Of Tau Bymentioning

confidence: 92%

Alzheimer-like Changes in Microtubule-associated Protein Tau Induced by Sulfated Glycosaminoglycans

Hasegawa¹,

Crowther

Jakes

et al. 1997

Journal of Biological Chemistry

198

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“…First, in vitro treatment with Z n 2 + induced neuronal cell death (5,6). Second, Zn 2 + , highly concentrated in synaptic vesicles of neurons (7), was shown to be translocated to degenerating postsynaptic neurons after cerebral ischemia or prolonged seizure (8,9). Finally, administration of a Zn 2 + chelator abrogated ischemic neuronal injury (10).…”

mentioning

confidence: 99%

Zinc as a paracrine effector in pancreatic islet cell death.

Kim

et al. 2000

Diabetes

100

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Because of a huge amount of Zn 2 + in secretory granules of pancreatic islet -cells, Zn 2 + released in certain conditions might affect the function or survival of islet cells. We studied potential paracrine effects of endogenous Zn 2 + on -cell death. Zn 2 + induced insulinoma/islet cell death in a dose-dependent manner. Chelation of released endogenous Zn 2 + by CaEDTA significantly decreased streptozotocin (STZ)-induced islet cell death in an in vitro culture system simulating in vivo circumstances but not in the conventional culture system. Z n 2 + chelation in vivo by continuous CaEDTA infusion significantly decreased the incidence of diabetes after STZ administration. N-( 6 -m e t h o x y -q u i n o l y l ) -p a r a -t o l u e n esulfonamide staining revealed that Zn 2 + was densely deposited in degenerating islet cells 24 h after STZ treatment, which was decreased by CaEDTA infusion. We show here that Zn 2 + is not a passive element for insulin storage but an active participant in islet cell death in certain conditions, which in time might contribute to the development of diabetes in aged people. D i a b e t e s 4 9 :3 6 7-372, 2000 C ertain central neurons and pancreatic islet -c e l l s contain a substantial amount of chelable zinc ion ( Z n 2 + ) (1,2). Neuronal Zn 2 + is co-secreted with neurotransmitters after excitation and might be involved in the modulation of ion channel activity (3,4). R e c e n t l y, reports indicating a role of endogenous Zn 2 + in neuronal death were published. First, in vitro treatment with Z n 2 + induced neuronal cell death (5,6). Second, Zn 2 + , highly concentrated in synaptic vesicles of neurons (7), was shown to be translocated to degenerating postsynaptic neurons after cerebral ischemia or prolonged seizure (8,9). Finally, administration of a Zn 2 + chelator abrogated ischemic neuronal injury (10). These findings suggest that Zn 2 + in synaptic vesicles may be causally related to neuronal death. Similar phenomena may occur in pancreatic -cells. Islet -cells contain even more Zn 2 + than do neurons. Zn 2 + in -cells, involved in the formation of insoluble insulin hexamer in secretory granules (11,12), is also co-secreted with insulin after stimulation with secretagogues (13). Zn 2 + released in certain conditions may have an impact on pancreatic -cells if significant local concentration is achieved. The current work was carried out to explore this possibility, focusing on the role of Zn 2 + in islet cell death. RESEARCH DESIGN AND METHODSCell culture. MIN6N8 cells, SV40-transformed insulinoma cells (14) (kindly provided by Prof. Miyazaki, Osaka University, Osaka, Japan), were cultured in Dulb e c c o 's modified Eagle's medium (DMEM) (GibcoBRL, Rockville, MD)-15% fetal calf serum (FCS). The effect of Zn 2 + was examined by culturing cells in the presence of ZnSO 4 . The presence of ZnSO 4 up to 1 mmol/l did not significantly affect pH of the culture medium. In experiments studying the effect of Zn 2 + without binding to proteins or amino acids, control salt solution (...

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“…The same neurons also secrete glutamate and are the so-called "gluzinergic" neurons found primarily in the mammalian cerebral cortex. Neurons store up to 300 M free zinc in their termini (3) and release it through several types of cation channels (e.g. N-methyl-D-aspartic acid receptors) when they are depolarized, reaching high concentrations that are known to cause acute neuronal death.…”

mentioning

confidence: 99%

Functional Interaction of Phosphatase and Tensin Homologue (PTEN) with the E3 Ligase NEDD4-1 during Neuronal Response to Zinc

Kwak

Wang

Pan

et al. 2010

Journal of Biological Chemistry

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The contribution of zinc-mediated neuronal death in the process of both acute and chronic neurodegeneration has been increasingly appreciated. Phosphatase and tensin homologue, deleted on chromosome 10 (PTEN), the major tumor suppressor and key regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, plays a critical role in neuronal death in response to various insults. NEDD4-1-mediated PTEN ubiquitination and subsequent degradation via the ubiquitin proteosomal system have recently been demonstrated to be the important regulatory mechanism for PTEN in several cancer types. We now demonstrate that PTEN is also the key mediator of the PI3K/Akt pathway in the neuronal response to zinc insult. We used primary cortical neurons and neuroblastoma N2a cells to show that zinc treatment results in a reduction of the PTEN protein level in parallel with increased NEDD4-1 gene/protein expression. The reduced PTEN level is associated with an activated PI3K pathway as determined by elevated phosphorylation of both Akt and GSK-3 as well as by the attenuating effect of a specific PI3K inhibitor (wortmannin). The reduction of PTEN can be attributed to increased protein degradation via the ubiquitin proteosomal system, as we show NEDD4-1 to be the major E3 ligase responsible for PTEN ubiquitination in neurons. Moreover, PTEN and NEDD4-1 appear to be able to counter-regulate each other to mediate the neuronal response to zinc. This reciprocal regulation requires the PI3K signaling pathway, suggesting a feedback loop mechanism. This study demonstrates that NEDD4-1-mediated PTEN ubiquitination is crucial in the regulation of PI3K/Akt signaling by PTEN during the neuronal response to zinc, which may represent a common mechanism in neurodegeneration.Zinc is increasingly recognized as an important molecule that plays both physiological and pathological roles in a variety of biological processes. The role of zinc in the central nervous system has also been discovered over the past 2 decades, as a neurotransmitter in modulating synaptic plasticity (1, 2). Although zinc is selectively stored in the pre-synaptic vesicles of a specific type of neuron, sequestered or tightly bound to cellular compartments, it can be rapidly released in response to extracellular signals. The same neurons also secrete glutamate and are the so-called "gluzinergic" neurons found primarily in the mammalian cerebral cortex. Neurons store up to 300 M free zinc in their termini (3) and release it through several types of cation channels (e.g. N-methyl-D-aspartic acid receptors) when they are depolarized, reaching high concentrations that are known to cause acute neuronal death. Together with glutamate, zinc mediates excitotoxicity, as manifested in acute brain injuries, ischemia, and seizures (4, 5). Zinc is also implicated in chronic neurodegenerative diseases such as Alzheimer disease via direct chelation with the amyloid precursor protein, thereby modulating its processing and generating oxidative stress (6).In cortical cell cultures, 100 M zinc, with ...

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Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat

Cited by 338 publications

References 29 publications

Alzheimer-like Changes in Microtubule-associated Protein Tau Induced by Sulfated Glycosaminoglycans

Alzheimer-like Changes in Microtubule-associated Protein Tau Induced by Sulfated Glycosaminoglycans

Zinc as a paracrine effector in pancreatic islet cell death.

Functional Interaction of Phosphatase and Tensin Homologue (PTEN) with the E3 Ligase NEDD4-1 during Neuronal Response to Zinc

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