Copper-dependent inhibition and oxidative inactivation with affinity cleavage of yeast glutathione reductase

Murakami, Keiko; Tsubouchi, Ryoko; Fukayama, Minoru; Yoshino, Masataka

doi:10.1007/s10534-014-9731-x

Cited by 17 publications

(11 citation statements)

References 23 publications

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“…GST inactivation was not due to cleavage of the enzyme (Fig. 6) as reported in the case of yeast glutathione reductase [33]. DTT treatment causes the aggregate to disintegrate and return GST to monomeric forms.…”

Section: Discussionsupporting

confidence: 60%

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Copper-Induced Inactivation of Camel Liver Glutathione S-Transferase

Ahmed

Malik

Jagirdar

et al. 2015

Biol Trace Elem Res

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Glutathione S-transferases (GSTs) are multifunctional enzymes and play an important role in detoxification of xenobiotics and protection against oxidative stress. Camel liver glutathione transferase (cGST) was recently isolated and characterized in our lab. In this study, we have evaluated the effect of monovalent, divalent, and trivalent cations on its activity and stability. Cu(++) was found to be the potent inhibitor of GST activity which loses complete activity at 0.5-mM concentration. Other metal ions did not inhibit GST even at higher concentration of 2 mM. GST incubated with Cu(++) (0.1 mM) resulted decrease in free sulfhydryl groups by 55%, whereas other metal ions did not show any effect on free thiol content. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed formation of GST aggregates instantly in the presence of Cu(++), which further increased in molecular size with increase in time of incubation. DTT treatment resulted in de-aggregation of GST oligomers to its monomeric form. However, the GST activity was not recovered completely after de-aggregation. Cu(++) was found to inhibit GST activity by accelerating the inter- and intra-disulfide bond formation. Far-UV circular dichroism (CD) results showed that Cu(++)-catalyzed air oxidation of sulfhydryl groups leads to minor conformational changes in the GST.

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Section: Discussionsupporting

confidence: 60%

“…Copper ions show high affinity for thiols and amino groups present in proteins. Their binding causes the alterations in the enzyme structure and hence inhibition of their activity [33]. Therefore, the oxidation by generation of ROS and protein binding are two different mechanisms of copper-induced modifications in the proteins.…”

Section: Introductionmentioning

confidence: 99%

Copper-Induced Inactivation of Camel Liver Glutathione S-Transferase

Ahmed

Malik

Jagirdar

et al. 2015

Biol Trace Elem Res

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“…proved that copper can bind to GR and cause it to be cleaved, but the binding sites of the GR for copper remains obscure. [ 34 ] Therefore, we investigated the effect of CuCs on GR activity. As shown in Figure 4F, levels of GSH in MRSA and E. coli were both decreased after treatment with CuCs.…”

Section: Resultsmentioning

confidence: 99%

Copper Clusters: An Effective Antibacterial for Eradicating Multidrug‐Resistant Bacterial Infection In Vitro and In Vivo

Zhang

Shu

et al. 2021

Adv Funct Materials

138

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Infections caused by multidrug-resistant (MDR) bacteria pose a threat to human health worldwide, making new effective antibacterial agents urgently desired. To date, it is still a great challenge to develop new antibiotics for MDR bacteria with clear antibacterial mechanisms. Herein, a novel alternative antibacterial copper clusters (CuCs) molecule is precisely synthesized utilizing an artificially designed theanine peptide. The prepared CuCs exhibit excellent broad-spectrum antibacterial activity in vitro, including gram-positive bacteria (methicillin-resistant Staphylococcus aureus [MRSA], Staphylococcus aureus, and Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). The robust antibacterial effect is due to its ability to not only destroy the bacterial wall structure, but also regulate the ratio of GSH/GSSG by inhibiting the activity of glutathione reductase, thus causing the outbreak of reactive oxygen species and ultimately leading to bacterial death. In addition, in vivo studies demonstrate that CuCs can significantly rescue skin wound infections and sepsis in mice caused by MRSA, and has the same therapeutic efficacy as mupirocin ointment and first-line clinically anchored anti-MRSA drug vancomycin. Moreover, CuCs exhibit extremely low cytotoxicity to normal mammalian cells compared to silver and platinum clusters. With further development and optimization, CuCs has great potential as a new class of antibacterial agents to fight antibiotic-resistant pathogens.

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“…Sulfite exposure was found to perturbate the striatal antioxidant system, reducing the activities of GPx, GR, GST, and G6PDH and decreasing GSH level, likely related to the overproduction of reactive species induced by this metabolite 9,11,12 . In this regard, it has been reported that hydrogen peroxide, peroxyl, hydroxyl, and superoxide radicals can cause oxidative attack to these protein structures leading to impaired activity 35‐38 . Also of note, glutathione S‐sulfonate, a compound originated from the lysis of GSSG by sulfite, has been shown to act as a competitive inhibitor of GST 39 …”

Section: Discussionmentioning

confidence: 99%

The mitochondrial‐targeted reactive species scavenger JP4‐039 prevents sulfite‐induced alterations in antioxidant defenses, energy transfer, and cell death signaling in striatum of rats

Glänzel

Grings

Rosa-Junior

et al. 2020

J of Inher Metab Disea

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Sulfite oxidase (SO) deficiency is a disorder caused either by isolated deficiency of SO or by defects in the synthesis of its molybdenum cofactor. It is characterized biochemically by tissue sulfite accumulation. Patients present with seizures, progressive neurological damage, and basal ganglia abnormalities, the pathogenesis of which is not fully established. Treatment is supportive and largely ineffective. To address the pathophysiology of sulfite toxicity, we examined the effects of intrastriatal administration of sulfite in rats on antioxidant defenses, energy transfer, and mitogen‐activated protein kinases (MAPK) and apoptosis pathways in rat striatum. Sulfite administration decreased glutathione (GSH) concentration and glutathione peroxidase, glucose‐6‐phosphate dehydrogenase, glutathione S‐transferase, and glutathione reductase activities in striatal tissue. Creatine kinase (CK) activity, a crucial enzyme for cell energy transfer, was also decreased by sulfite. Superoxide dismutase‐1 (SOD1) and catalase (CAT) proteins were increased, while heme oxygenase‐1 (HO‐1) was decreased. Additionally, sulfite altered phosphorylation of MAPK by decreasing of p38 and increasing of ERK. Sulfite further augmented the content of GSK‐3β, Bok, and cleaved caspase‐3, indicating increased apoptosis. JP4‐039 is a mitochondrial‐targeted antioxidant that reaches higher intramitochondrial levels than other traditional antioxidants. Intraperitoneal injection of JP4‐039 before sulfite administration preserved activity of antioxidant enzymes and CK. It also prevented or attenuated alterations in SOD1, CAT, and HO‐1 protein content, as well as changes in p38, ERK, and apoptosis markers. In sum, oxidative stress and apoptosis induced by sulfite injection are prevented by JP4‐039, identifying this molecule as a promising candidate for pharmacological treatment of SO‐deficient patients.

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Copper-dependent inhibition and oxidative inactivation with affinity cleavage of yeast glutathione reductase

Cited by 17 publications

References 23 publications

Copper-Induced Inactivation of Camel Liver Glutathione S-Transferase

Copper-Induced Inactivation of Camel Liver Glutathione S-Transferase

Copper Clusters: An Effective Antibacterial for Eradicating Multidrug‐Resistant Bacterial Infection In Vitro and In Vivo

The mitochondrial‐targeted reactive species scavenger JP4‐039 prevents sulfite‐induced alterations in antioxidant defenses, energy transfer, and cell death signaling in striatum of rats

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