Redox systems of the cell: Possible links and implications

Das, Kumuda C.; White, Carl W.

doi:10.1073/pnas.162369199

Cited by 62 publications

(41 citation statements)

References 44 publications

(29 reference statements)

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“…Interestingly, this species appears to be stable even at quite fast scan rates (,,~100 mV s -t) suggesting that the radical is localized on the sulfur atom or perhaps delocalised between the two sulfur atoms. This is contrary to previous suggestions [4] that a carbon centred radical is implicated. Although, the formation of the radical intermediate between oxidised (disulfide) and reduced (dithiolate) trx forms is reversible, the fully reduced dithiolate is electrochemically irreversible.…”

Section: Discussioncontrasting

confidence: 99%

“…The most ubiquitous of these is thioredoxin (trx) [1][2][3][4]. This multifunctional protein performs an extraordinary range of functions which include; regulation of cellular signalling, protein activation, gene transcription and oxidative stress in eukaryotic cells [3,4]. Trx is a redox-active protein of mass ~12 kDa with two highly conserved catalytic cysteines within the sequence -Cys-Gly-Pro-Cys- [1,3].…”

Section: Introductionmentioning

confidence: 99%

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Probing the stability of the disulfide radical intermediate of thioredoxin using direct electrochemistry

et al. 2003

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SummaryThioredoxin, a redox active disulfide protein, has been specifically immobilized at a modified gold electrode. The thioredoxin is uniquely oriented relative to the electrode surface via a histidine tag thereby enabling the redox mechanism of protein to be examined. When scanning the applied potential in the negative direction (cathodic), two one-electron reduction waves can be observed. The first of these redox waves occurs at -90 mV and is electrochemically reversible at all scan rates whereas the second wave occurs at -433 mV is irreversible. These two processes are interpreted as the initial reduction of the disulfide form of the protein to a stable (reversible) semi-reduced radical anion intermediate, followed by an electrochemically irreversible process to form a fully reduced thioredoxin. These electron transfer characteristics suggest that a radical intermediate retaining the sulfur-sulfur bond is thermodynamically stable but the addition of a second electron results in bond scission.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Probing the stability of the disulfide radical intermediate of thioredoxin using direct electrochemistry

et al. 2003

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“…36 We found an isoform of thioredoxin 2, thioredoxin domain-con- Drug-näive schizophrenia patients are denoted by **(n ¼ 7), while minimally treated patients are marked by *(o6000 lifetime fluphenazine units; n ¼ 4). Note that the schizophrenia group appears to fall into two subclusters with respect to lowered transcript expression as indicated by the prominent blue shading.…”

Section: D-digementioning

confidence: 98%

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress

et al. 2004

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The etiology and pathophysiology of schizophrenia remain unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.

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“…Nrf2, in response to CS, regulates genes involved in two major redox systems, the glutathione and thioredoxin systems (25,26). Enzymes involved in glutathione synthesis (γ-GCS catalytic and regulatory subunits), members of the GST family, GSR, GPx2, GPx3, and genes that constitute the thioredoxin system (TrxR and Prx-1) were all induced in the lungs of Nrf2 +/+ mice in response to CS.…”

Section: Figurementioning

confidence: 99%

Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke–induced emphysema in mice

Rangasamy¹,

Cho²,

Thimmulappa³

et al. 2004

J. Clin. Invest.

481

435

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Although inflammation and protease/antiprotease imbalance have been postulated to be critical in cigarette smoke-induced (CS-induced) emphysema, oxidative stress has been suspected to play an important role in chronic obstructive pulmonary diseases. Susceptibility of the lung to oxidative injury, such as that originating from inhalation of CS, depends largely on its upregulation of antioxidant systems. Nuclear factor, erythroidderived 2, like 2 (Nrf2) is a redox-sensitive basic leucine zipper protein transcription factor that is involved in the regulation of many detoxification and antioxidant genes. Disruption of the Nrf2 gene in mice led to earlier-onset and more extensive CS-induced emphysema than was found in wild-type littermates. Emphysema in Nrf2-deficient mice exposed to CS for 6 months was associated with more pronounced bronchoalveolar inflammation; with enhanced alveolar expression of 8-oxo-7,8-dihydro-2′-deoxyguanosine, a marker of oxidative stress; and with an increased number of apoptotic alveolar septal cells -predominantly endothelial and type II epithelial cells -as compared with wild-type mice. Microarray analysis identified the expression of nearly 50 Nrf2-dependent antioxidant and cytoprotective genes in the lung that may work in concert to counteract CS-induced oxidative stress and inflammation. The responsiveness of the Nrf2 pathway may act as a major determinant of susceptibility to tobacco smoke-induced emphysema by upregulating antioxidant defenses and decreasing lung inflammation and alveolar cell apoptosis.

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Redox systems of the cell: Possible links and implications

Cited by 62 publications

References 44 publications

Probing the stability of the disulfide radical intermediate of thioredoxin using direct electrochemistry

Probing the stability of the disulfide radical intermediate of thioredoxin using direct electrochemistry

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress

Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke–induced emphysema in mice

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