The Chemical Basis of Biological Redox Control

Jacob, Claus; Doering, Mandy; Burkholz, Torsten

doi:10.1002/9783527627585.ch4

Cited by 6 publications

(5 citation statements)

References 131 publications

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“…Because coordination of Mn II to N4Py does not appear to be favorable and Mn II is readily exchanged for Fe II , it is likely that mainly metal exchange, forming the Fe II -N4Py complex, is responsible for the observed intracellular activity. In addition, Zn II is not redox-active …”

Section: Resultsmentioning

confidence: 99%

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Importance of Metal-Ion Exchange for the Biological Activity of Coordination Complexes of the Biomimetic Ligand N4Py

et al. 2018

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Metal coordination complexes can display interesting biological activity, as illustrated by the bleomycins (BLMs), a family of natural antibiotics that when coordinated to a redox-active metal ion, show antitumor activity. Yet, which metal ion is required for the activity in cells is still subject to debate. In this study, we described how different metal ions affect the intracellular behavior and activity of the synthetic BLM-mimic N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine (N4Py). Our study shows that a mixture of iron(II), copper(II), and zinc(II) complexes can be generated when N4Py is added to cell cultures but that the metal ion can also be exchanged by other metal ions present in cells. Moreover, the combination of chemical data, together with the performed biological experiments, shows that the active complex causing oxidative damage to cells is the FeII-N4Py complex and not per se the metal complex that was initially added to the cell culture medium. Finally, it is proposed that the high activity observed upon the addition of the free N4Py ligand is the result of a combination of scavenging of biologically relevant metals and oxidative damage caused by the iron(II) complex.

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Section: Resultsmentioning

confidence: 99%

“…In addition, Zn II is not redox-active. 78 (iv) Both iron(II) and iron(III) complexes are very active in the cleavage of supercoiled pUC18 plasmid DNA. The similarity in the cleavage activity is expected because the presence of a large excess of DTT will force the ferric complex into a ferrous complex.…”

Section: Inorganic Chemistrymentioning

confidence: 99%

Importance of Metal-Ion Exchange for the Biological Activity of Coordination Complexes of the Biomimetic Ligand N4Py

et al. 2018

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“…In cells, the estimated steady state concentration and half-life of this species is 100 pM–5 nM and ∼0.1–2 s, respectively. 234 Although • NO is more stable than H 2 O 2 in cells, protein and small molecule NO-donors are believed to be a relevant source of • NO in biological systems. In general, • NO is a modestly reactive radical and does not inflict indiscriminate damage on biomolecules.…”

Section: Reactive Nitrogen Species (Rns) In Biological Systemsmentioning

confidence: 99%

Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

2013

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“…However, under pathological conditions, the balance is impaired, thus resulting in a disturbance of cell redox state that can affect the structure and function of cell components. Under conditions of oxidative stress (OxS), protection of cysteine residues against irreversible oxidation is fundamental to block further damage on protein structure and function [ 5 ]. The mechanism of protection is S-glutathionylation, a reversible S-thiolation reaction leading to the formation of a mixed disulfide between protein cysteine residue and glutathione.…”

Section: Introductionmentioning

confidence: 99%

Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation

et al. 2020

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Reactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible oxidative damages. A fundamental player in this fine balance is reduced glutathione (GSH), required for the scavenging of ROS as well as of the reactive 2-oxoaldehydes methylglyoxal (MGO). MGO is a cytotoxic compound formed constitutively as byproduct of nutrient catabolism, and in particular of glycolysis, detoxified in a GSH-dependent manner by the glyoxalase pathway consisting in glyoxalase I and glyoxalase II reactions. A physiological increase in ROS production (oxidative eustress, OxeS) is promptly signaled by the decrease of cellular GSH/GSSG ratio which can induce the reversible S-glutathionylation of key proteins aimed at restoring the redox balance. An increase in MGO level also occurs under oxidative stress (OxS) conditions probably due to several events among which the decrease in GSH level and/or the bottleneck of glycolysis caused by the reversible S-glutathionylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. In the present review, it is shown how MGO can play a role as a stress signaling molecule in response to OxeS, contributing to the coordination of cell metabolism with gene expression by the glycation of specific proteins. Moreover, it is highlighted how the products of MGO metabolism, S-D-lactoylglutathione (SLG) and D-lactate, which can be taken up and metabolized by mitochondria, could play important roles in cell response to OxS, contributing to cytosol-mitochondria crosstalk, cytosolic and mitochondrial GSH pools, energy production, and the restoration of the GSH/GSSG ratio. The role for SLG and glyoxalase II in the regulation of protein function through S-glutathionylation under OxS conditions is also discussed. Overall, the data reported here stress the need for further studies aimed at understanding what role the evolutionary-conserved MGO formation and metabolism can play in cell signaling and response to OxS conditions, the aberration of which may importantly contribute to the pathogenesis of diseases associated to elevated OxS.

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The Chemical Basis of Biological Redox Control

Cited by 6 publications

References 131 publications

Importance of Metal-Ion Exchange for the Biological Activity of Coordination Complexes of the Biomimetic Ligand N4Py

Importance of Metal-Ion Exchange for the Biological Activity of Coordination Complexes of the Biomimetic Ligand N4Py

Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation

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