Hydroxyl Radical Formation from Cuprous Ion and Hydrogen Peroxide: A Spin-Trapping Study

Gunther, Michael R.; Hanna, Phillip M.; Mason, Ronald P.; Cohen, Myron S.

doi:10.1006/abbi.1995.1068

Cited by 176 publications

(105 citation statements)

References 0 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Both Cu and Fe are transition metals and can generate OH' through interaction with H,O, (Southorn and Powis, 1988). Therefore, the increased Cu toxicity is not due to increased H,O, and subsequent CU/H,O,-generated OH' alone (Gunther et al, 1995), as a similar effect would be expected in Fe-treated cultures. There are, however, differences in the reactive potential between Cu and Fe in biological systems (Spencer et al, 1994).…”

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

“…An important consequence of increased oxidative stress in neurons may involve the toxic interaction between ROS and the transition metal copper (Cu) (Gunther et al, 1995). The interaction between H202 and Cu can potentially result in generation of the highly toxic OH' (Gunther et al, 1995): Cu (I) + H z 0 2 + Cu (11) + OH' + OH- (1) Cu may have a central role in several neurodegenerative disorders, including AD, CJD, and ALS. High levels of Cu have been detected in AD-associated plaques (Love11 et al, 1998) and can interact with both amyloid-/3 (AP) (Atwood et al, 1998;Bondy et al, 1998; A.I.B., unpublished observations) and amyloid precursor protein (APP) (Hesse et al, 1994;Multhaup et al, 1996Multhaup et al, , 1998.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

White

Bush

Beyreuther

et al. 1999

Journal of Neurochemistry

View full text Add to dashboard Cite

Perturbations to glutathione (GSH) metabolism may play an important role in neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases. A primary function of GSH is to prevent the toxic interaction between free radicals and reactive transition metals such as copper (Cu). Due to the potential role of Cu in neurodegeneration, we examined the effect of GSH depletion on Cu toxicity in murine primary neuronal cultures. Depletion of cellular GSH with L-buthionine-[S,R]-sulfoximine resulted in a dramatic potentiation of Cu toxicity in neurons without effect on iron (Fe) toxicity. Similarly, inhibition of glutathione reductase (GR) activity with 1,3-bis(2-chloroethyl)-l -nitrosurea also increased Cu toxicity in neurons. To determine if the Alzheimer's amyloid-p (Ap) peptide can affect neuronal resistance to transition metal toxicity, we exposed cultures to nontoxic concentrations of Ap25-35 in the presence or absence of Cu or Fe. Ap25-35 pretreatment was found to deplete neuronal GSH and increase GR activity, confirming the ability of Ap to perturb neuronal GSH homeostasis.Ap25-35 pretreatment potently increased Cu toxicity but had no effect on Fe toxicity. These studies demonstrate an important role for neuronal GSH homeostasis in selective protection against Cu toxicity, a finding with widespread implications for neurodegenerative disorders.

show abstract

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

White

Bush

Beyreuther

et al. 1999

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…15 As a result, copper has been shown to cause oxidative damage to proteins, lipids, and nucleic acids. [16][17][18][19][20] Further, increased levels of hydroperoxides have been reported in a human glial cell line treated with excess copper. 21 Copper has also been shown to cause a reduction in the activities of mitochondrial enzymes and depletion of ATP, and such changes were attenuated by pretreatment with antioxidants.…”

mentioning

confidence: 99%

The mitochondrial permeability transition, and oxidative and nitrosative stress in the mechanism of copper toxicity in cultured neurons and astrocytes

Reddy

Rao

Norenberg

2008

Laboratory Investigation

View full text Add to dashboard Cite

Copper is an essential element and an integral component of various enzymes. However, excess copper is neurotoxic and has been implicated in the pathogenesis of Wilson's disease, Alzheimer's disease, prion conditions, and other disorders. Although mechanisms of copper neurotoxicity are not fully understood, copper is known to cause oxidative stress and mitochondrial dysfunction. As oxidative stress is an important factor in the induction of the mitochondrial permeability transition (mPT), we determined whether mPT plays a role in copper-induced neural cell injury. Cultured astrocytes and neurons were treated with 20 mM copper and mPT was measured by changes in the cyclosporin A (CsA)-sensitive inner mitochondrial membrane potential (DCm), employing the potentiometric dye TMRE. In astrocytes, copper caused a 36% decrease in the DCm at 12 h, which decreased further to 48% by 24 h and remained at that level for at least 72 h. Cobalt quenching of calcein fluorescence as a measure of mPT similarly displayed a 45% decrease at 24 h. Pretreatment with antioxidants significantly blocked the copper-induced mPT by 48-75%. Copper (24 h) also caused a 30% reduction in ATP in astrocytes, which was completely blocked by CsA. Copper caused death (42%) in astrocytes by 48 h, which was reduced by antioxidants (35-60%) and CsA (41%). In contrast to astrocytes, copper did not induce mPT in neurons. Instead, it caused early and extensive death with a concomitant reduction (63%) in ATP by 14 h. Neuronal death was prevented by antioxidants and nitric oxide synthase inhibitors but not by CsA. Copper increased protein tyrosine nitration in both astrocytes and neurons. These studies indicate that mPT, and oxidative and nitrosative stress represent major factors in copper-induced toxicity in astrocytes, whereas oxidative and nitrosative stress appears to play a major role in neuronal injury.

show abstract

“…Copper, like Fe, is redox active and can serve as a catalyst for the formation of toxic oxidant species such as the hydroxyl radical (67). It has been suggested that formation of such oxidant species may be involved in the ability of these metals to increase Fe acquisition in some cells (18,20).…”

Section: Discussionmentioning

confidence: 99%

Multivalent Metal-Induced Iron Acquisition from Transferrin and Lactoferrin by Myeloid Cells

Olakanmi

Rasmussen

Lewis

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

We previously described a unique, high-capacity, ATP-independent mechanism through which myeloid cells acquire Fe from low-m.w. chelates. The rate of this Fe acquisition is markedly increased by cellular exposure to multivalent metal cations. Because most Fe in vivo is bound to transferrin or lactoferrin, we examined whether this mechanism also contributes to myeloid cell acquisition of Fe from transferrin and/or lactoferrin. Using HL-60 cells as a model system, we show cellular acquisition of 59Fe from both lactoferrin and transferrin that was unaffected by conditions that depleted the cells of ATP or disrupted their cytoskeleton. Fe acquisition was dramatically increased by cell exposure to various metals including Ga3+, Gd3+, Al3+, Fe3+, La3+, Zr4+, Sn4+, Cu2+, and Zn2+ by a process that was reversible. Exposure to these same metals also increased binding of both transferrin and lactoferrin to the cell surface by a process that does not appear to involve the well-described plasma membrane receptor for transferrin. Approximately 60% of the Fe acquired by the cells from transferrin and lactoferrin remained cell associated 18 h later. HL-60 cells possess a high-capacity multivalent metal-inducible mechanism for Fe acquisition from transferrin and lactoferrin that bears many similarities to the process previously described that allows these and other cell types to acquire Fe from low-m.w. Fe chelates. The biologic importance of this mechanism may relate to its high Fe acquisition capacity and the speed with which it is able to rapidly adapt to the level of extracellular Fe.

show abstract

Hydroxyl Radical Formation from Cuprous Ion and Hydrogen Peroxide: A Spin-Trapping Study

Cited by 176 publications

References 0 publications

Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

The mitochondrial permeability transition, and oxidative and nitrosative stress in the mechanism of copper toxicity in cultured neurons and astrocytes

Multivalent Metal-Induced Iron Acquisition from Transferrin and Lactoferrin by Myeloid Cells

Contact Info

Product

Resources

About