Copper(I) transfer into metallothionein mediated by glutathione

Ferreira, Arturo; Ciriolo, Maria Rosa; Marcocci, Lucia; Rotilio, Giuseppe

doi:10.1042/bj2920673

Cited by 107 publications

(55 citation statements)

References 33 publications

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“…Glutathione also plays an important role in Cu sequestration and detoxification in vivo (40,42,43). In cell-free systems, Cu(I) complexes of GSH have been shown to transfer Cu to both metallothionein (47) and to SOD1 (37)(38)(39). As such, it is possible that Cu(I)-GSH may also serve as a Cu donor for human SOD1 in vivo.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone

Carroll

Girouard

Ulloa

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

168

201

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The Cu- and Zn-containing superoxide dismutase 1 (SOD1) largely obtains Cu in vivo by means of the action of the Cu chaperone CCS. Yet, in the case of mammalian SOD1, a secondary pathway of activation is apparent. Specifically, when human SOD1 is expressed in either yeast or mammalian cells that are null for CCS, the SOD1 enzyme retains a certain degree of activity. This CCS-independent activity is evident with both wild-type and mutant variants of SOD1 that have been associated with familial amyotrophic lateral sclerosis. We demonstrate here that the CCS-independent activation of mammalian SOD1 involves glutathione, particularly the reduced form, or GSH. A role for glutathione in CCS-independent activation was seen with human SOD1 molecules that were expressed in either yeast cells or immortalized fibroblasts. Compared with mammalian SOD1, the Saccharomyces cerevisiae enzyme cannot obtain Cu without CCS in vivo, and this total dependence on CCS involves the presence of dual prolines near the C terminus of the SOD1 polypeptide. Indeed, the insertion of such prolines into human SOD1 rendered this molecule refractory to CCS-independent activation. The possible implications of multiple pathways for SOD1 activation are discussed in the context of SOD1 evolutionary biology and familial amyotrophic lateral sclerosis

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Section: Discussionmentioning

confidence: 99%

Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone

Carroll

Girouard

Ulloa

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

168

201

View full text Add to dashboard Cite

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“…An alternative explanation is that depletion of GSH results in greater intracellular levels of highly reactive unbound Cu that are able to generate further toxic ROS. This is supported by studies showing GSH to be important for cellular Cu transport, detoxification, and sequestration to metalloproteins and to the important antioxidant enzyme CuIZn SOD (Freedman et al, 1989;Ferreira et al, 1993;Vulpe and Packman, 1995). The role of free radicals in Cu toxicity was confirmed by abolition of toxicity using the H,O, and 0,-scavenger MnTMPyP (Day et al, 1997).…”

Section: Discussionmentioning

confidence: 92%

“…This tripeptide is critical for removal of H202 and prevention against and repair of lipid and protein oxidation (Mark et id., 1997) and is an important Cu transport and detoxification molecule (Freedman e t al., 1989;Ferreira et al, 1993;Vulpe and Packman, 1995). GSH levels are maintained by a complex pathway involving y-glutamylcysteine synthetase (GS; EC 6.3.2.2), glutathione peroxidase (GPx; EC 1.1 1.1.9), and glutathione reductase (GR; EC 1.6.4.2) (Bains and Shaw, 1997 …”

mentioning

confidence: 99%

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

White

Bush

Beyreuther

et al. 1999

Journal of Neurochemistry

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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.

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“…It has long been suggested that reduced glutathione (GSH) may participate in intracellular Cu homeostasis by forming Cu-GSH complexes when transferring Cu to CSD (Ciriolo et al, 1990) and metallothionein (Ferreira et al, 1993) in vitro. GSH was required for CCS-independent activation of hSOD1 in yCCS mutant strains with defective GSH metabolism, and wSod-1 was inactive in the presence of CCS when GSH was depleted in yeast (Carroll et al, 2004;Jensen and Culotta, 2005).…”

mentioning

confidence: 99%

Copper Chaperone-Dependent and -Independent Activation of Three Copper-Zinc Superoxide Dismutase Homologs Localized in Different Cellular Compartments in Arabidopsis

et al. 2011

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Superoxide dismutases (SODs) are important antioxidant enzymes that catalyze the disproportionation of superoxide anion to oxygen and hydrogen peroxide to guard cells against superoxide toxicity. The major pathway for activation of copper/zinc SOD (CSD) involves a copper chaperone for SOD (CCS) and an additional minor CCS-independent pathway reported in mammals. We characterized the CCS-dependent and -independent activation pathways for three CSDs localized in different cellular compartments in Arabidopsis (Arabidopsis thaliana). The main activation pathway for CSD1 in the cytoplasm involved a CCS-dependent and -independent pathway, which was similar to that for human CSD. Activation of CSD2 in chloroplasts depended totally on CCS, similar to yeast (Saccharomyces cerevisiae) CSD. Peroxisome-localized CSD3 via a CCS-independent pathway was similar to nematode (Caenorhabditis elegans) CSD in retaining activity in the absence of CCS. In Arabidopsis, glutathione played a role in CCS-independent activation, as was reported in humans, but an additional factor was required. These findings reveal a highly specific and sophisticated regulation of CSD activation pathways in planta relative to other known CCS-independent activation.

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Copper(I) transfer into metallothionein mediated by glutathione

Cited by 107 publications

References 33 publications

Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone

Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone

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

Copper Chaperone-Dependent and -Independent Activation of Three Copper-Zinc Superoxide Dismutase Homologs Localized in Different Cellular Compartments in Arabidopsis

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