Zinc and Copper inhibit nerve growth factor-mediated protection from oxidative stress-induced apoptosis

Wang, Wei; Post, Joan I.; Dow, Kimberly; Shin, Seon H.; Riopelle, Richard J.; Ross, Gregory M.

doi:10.1016/s0304-3940(98)00929-x

Cited by 37 publications

(36 citation statements)

References 18 publications

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“…To the best of our knowledge, the coordination features of metal-ion complexes with NGF have been determined only by theoretical methods. [16][17][18] The computational results suggest a model in which Zn 2 + alters the conformation of NGF by forming a pentacoordinate complex. This metal ion has been found to bind to the imidazole nitrogen atoms of His4 and His8 of one monomer and to the imidazole nitrogen atom of His84 and both oxygen atoms of Asp105 of the other unit of the NGF dimer; [16,17] the same coordination environment has been proposed for Cu 2 + .…”

Section: Introductionmentioning

confidence: 91%

“…[15] Thus, it is conceivable that transition-metal ions could play selective physiological/pathological roles by modulating NGF activity. [16][17][18][19][20][21][22] High concentrations of Zn 2 + and Cu 2 + have been shown to inhibit the in vitro effects of NGF as well as other neurotrophins (brain-derived neurotrophic factor (BDNF), neurotrophin-3 and neurotrophin-4/5). In addition to the decrease in cell viability, due to the inhibition of the trophic signalling of NGF after interaction with TrkA receptors, [19] Zn 2 + and Cu 2 + have been reported to inhibit NGF-mediated protection from oxidative-stress-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the decrease in cell viability, due to the inhibition of the trophic signalling of NGF after interaction with TrkA receptors, [19] Zn 2 + and Cu 2 + have been reported to inhibit NGF-mediated protection from oxidative-stress-induced apoptosis. [17] Zn 2 + (10-300 mm) has been shown to slightly inhibit TrkB phosphorylation caused by exposure to BDNF in cortical culture systems, whereas similar amounts of the same metal ion activate TrkB when administered without BDNF. [23] Furthermore, Zn 2 + can induce pro-BDNF release in a metalloproteinase-dependent mode, which leads to increased mature BDNF levels in the cell culture medium.…”

Section: Introductionmentioning

confidence: 99%

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The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu²⁺ and Zn²⁺ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

Travaglia

Arena

Fattorusso³

et al. 2011

Chemistry A European J

101

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There is a significant overlap between brain areas with Zn(2+) and Cu(2+) pathological dys-homeostasis and those in which the nerve growth factor (NGF) performs its biological role. The protein NGF is necessary for the development and maintenance of the sympathetic and sensory nervous systems. Its flexible N-terminal region has been shown to be a critical domain for TrkA receptor binding and activation. Computational analyses show that Zn(2+) and Cu(2+) form pentacoordinate complexes involving both the His4 and His8 residues of the N-terminal domain of one monomeric unit and the His84 and Asp105 residues of the other monomeric unit of the NGF active dimer. To date, neither experimental data on the coordination features have been reported, nor has one of the hypotheses according to which Zn(2+) and Cu(2+) may have different binding environments or the Ser1 α-amino group could be involved in coordination been supported. The peptide fragment, encompassing the 1-14 sequence of the human NGF amino-terminal domain (NGF(1-14)), blocked at the C terminus, was synthesised and its Cu(2+) and Zn(2+) complexes characterized by means of potentiometric and spectroscopic (UV/Vis, CD, NMR, and EPR) techniques. The N-terminus-acetylated form of NGF(1-14) was also investigated to evaluate the involvement of the Ser1 α-amino group in metal-ion coordination. Our results demonstrate that the amino group is the first anchoring site for Cu(2+) and is involved in Zn(2+) coordination at physiological pH. Finally, a synergic proliferative activity of both NGF(1-14) and the whole protein on SHSY5Y neuroblastoma cell line was found after treatment in the presence of Cu(2+). This effect was not observed after treatment with the N-acetylated peptide fragment, demonstrating a functional involvement of the N-terminal amino group in metal binding and peptide activity.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu²⁺ and Zn²⁺ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

Travaglia

Arena

Fattorusso³

et al. 2011

Chemistry A European J

101

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“…24 Zinc has previously been shown to block NGF-mediated neurite outgrowth in chick dorsal root ganglia (DRG), and rescue pheochromocytoma (PC12) cells from oxidative stress. 30,31 Both effects are mediated via the TrkA receptor. Theoretical studies have predicted that the ability of NGF to bind to p75 NTR can be attenuated in the presence of Zn 2+ and other transition metal cations, 32 and Zn 2+ blocks binding to`low affinity' p75 NTR .…”

Section: Introductionmentioning

confidence: 99%

Zinc inhibits p75NTR-mediated apoptosis in chick neural retina

et al. 2001

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It has previously been documented that Zn 2+ inhibits TrkAmediated effects of NGF. To evaluate the ability of Zn 2+ to attenuate the biological activities of NGF mediated by p75 NTR , we characterized the effects of this transition metal cation on both binding and the pro-apoptotic properties of the NGFp75 NTR interaction. Binding of NGF to p75 NTR displayed higher affinity in embryonic chick retinal cells than in PC12 cells. NGF induced apoptosis in dissociated cultures of chick neural retina. The addition of 100 mM Zn 2+ inhibited binding and chemical cross-linking of 125 I-NGF to p75 NTR , and also attenuated apoptosis mediated by this ligand-receptor interaction. These studies lead to the conclusion that Zn 2+ antagonizes NGF/p75 NTR -mediated signaling, suggesting that the effect of this transition metal cation can be either pro-or anti-apoptotic depending on the cellular context. Cell Death and Differentiation (2001) 8, 451 ± 456.

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“…Similarly, X-ray diffraction analysis indicates that 2.5S NGF has a zinc-binding site with His 84 /Asp 105 as ligands [11]. It has been suggested that zinc ion play a role in the structure and the biological activity of 2.5S NGF [11], although addition of extra Zn(II) to native 2.5S NGF could result in its inactivation [12][13][14]. However, little attention has been paid to the role of Zn(II) in native 2.5S NGF.…”

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confidence: 99%

Effect of Zn(II) on the Structure and Biological Activity of Natural β-NGF

Zhao

Yü

et al. 2004

ABBS

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Only β-NGF, the subunit of the 7S NGF complex, exhibits NGF activity, but the function of the zinc ion in native β-NGF has received little attention. Flameless atomic absorption spectroscopy (FAAS) measurements reveal that native β-NGF contains Zn(II) with a Zn(II)/β-NGF stoichiometry of 1:14.6. The presence of Zn(II) in the native molecule results in significant changes of the secondary structure and local tertiary structure around Trp(s) with respect to those of apo β-NGF, as suggested by spectra of fluorescence and circular dichrosim. Stopped-flow studies show that there are at least two steps during the interaction of Zn(II) with the apo form. In comparison with its apo form, the native β-NGF shows a higher ability to trigger the proliferation of TF1 cells and mediate the survival of PC12. Thus it is most likely that the structural changes caused by the presence of Zn(II) directly lead to the increase in the biological activity of β-NGF. All results indicate that Zn(II) in native β-NGF plays an important role in the structure and the biological activity of the protein.

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Zinc and Copper inhibit nerve growth factor-mediated protection from oxidative stress-induced apoptosis

Cited by 37 publications

References 18 publications

The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu²⁺ and Zn²⁺ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu²⁺ and Zn²⁺ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

Zinc inhibits p75NTR-mediated apoptosis in chick neural retina

Effect of Zn(II) on the Structure and Biological Activity of Natural β-NGF

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Zinc and Copper inhibit nerve growth factor-mediated protection from oxidative stress-induced apoptosis

Cited by 37 publications

References 18 publications

The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu2+ and Zn2+ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu2+ and Zn2+ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

Zinc inhibits p75NTR-mediated apoptosis in chick neural retina

Effect of Zn(II) on the Structure and Biological Activity of Natural &beta;-NGF

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The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu²⁺ and Zn²⁺ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

The Inorganic Perspective of Nerve Growth Factor: Interactions of Cu²⁺ and Zn²⁺ with the N‐Terminus Fragment of Nerve Growth Factor Encompassing the Recognition Domain of the TrkA Receptor

Effect of Zn(II) on the Structure and Biological Activity of Natural β-NGF