Human erythrocytes exposure to juglone leads to an increase of superoxide anion production associated with cytochrome b5 reductase uncoupling

Valério, Gabriel N.; Gutiérrez‐Merino, Carlos; Nogueira, Fátima; Moura, Isabel; Moura, José J. G.; Samhan-Arias, Alejandro K.

doi:10.1016/j.bbabio.2019.148134

Cited by 5 publications

(13 citation statements)

References 62 publications

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“…Semiquinone generation has been proposed to be key for the formation of ROS [ 49 ]. This is also supported by experiments showing that the formation of CoQ semiquinone radical and recycling of vitamin E homologs are O 2 •− -dependent reactions, which agree with the ability of C b 5 R to produce O 2 •− [ 20 , 28 , 31 , 33 ]. In addition, the formation of ROS in biological systems depends on the reaction between ubiquinol and electron partners accepting two electrons leading to the formation of oxidized CoQ.…”

Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rsupporting

confidence: 66%

“…NQO1 also reduces CoQ through a two-electron reaction mechanism using both NADH and NADPH [ 48 ]. This difference between both systems may be significant under oxidative stress conditions since the formation of the semiquinone radical could lead to the production of O 2 •− upon by its reaction with molecular oxygen, as reported, by the mitochondrial redox chain and, also found by C b 5 R reacting with CoQ mimetics [ 28 ]. The semiquinone radical and possible deleterious side reactions can be avoided by C b 5 R recycling the semiquinone radical, reducing the radical rather than reducing it after generation of the oxidized quinone.…”

Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rmentioning

confidence: 95%

“…The presence of a transmembrane domain in charge of H 2 O 2 production associated with the E-loop [ 26 ] suggests that indeed this enzyme NOX4 might work as a redox-signaling transducer. Additionally, NOX4–C b 5 R complexes seem necessary for proper coupling between both enzymes, because excessive ubiquinol oxidation has been reported to generate H 2 O 2 and O 2 •− [ 27 , 28 , 29 , 30 ]. Notably, the importance of correct clustering of C b 5 R with other proteins or associated with a correct membrane environment has been pointed out in the plasma membrane of neurons [ 19 , 31 , 32 , 33 ].…”

Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rmentioning

confidence: 99%

“…A role regarding an in situ cholesterol formation at this location should not be discarded based on C b 5 functions in the last steps of cholesterol synthesis [ 9 , 15 ]. We have reported that C b 5 R/C b 5 can be a source of reactive oxygen species using the purified enzyme, biological membranes, and culture cells [ 28 , 31 , 33 ]. Cholesterol-rich plasma membrane sub microdomains have been suggested to be a major extramitochondrial O 2 •− source in cerebellar granule cells cultures [ 32 ].…”

Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rmentioning

confidence: 99%

“…For example, two reductase conformations were characterized by experiments performed at alkaline pHs, a strategy that we also used to describe the novel enzymatic activities of C b 5 [ 71 , 72 ]. Additionally, a second inactive swollen form in which at least a cysteine and a tyrosine residue are exposed can be stabilized by the addition of mersalyl, a C b 5 R inhibitor [ 28 ]. These changes support the existence of altered conformations associated with the binding of certain ligands in vivo and by changes in the ionization of the lateral side chain of some amino acid residues.…”

Section: Intramolecular Dynamics Of C B 5 Rmentioning

confidence: 99%

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Structural Features of Cytochrome b5–Cytochrome b5 Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome b5 Reductase

Gutiérrez‐Merino

Martı́nez-Costa

Monsalve

et al. 2021

IJMS

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Membrane cytochrome b5 reductase is a pleiotropic oxidoreductase that uses primarily soluble reduced nicotinamide adenine dinucleotide (NADH) as an electron donor to reduce multiple biological acceptors localized in cellular membranes. Some of the biological acceptors of the reductase and coupled redox proteins might eventually transfer electrons to oxygen to form reactive oxygen species. Additionally, an inefficient electron transfer to redox acceptors can lead to electron uncoupling and superoxide anion formation by the reductase. Many efforts have been made to characterize the involved catalytic domains in the electron transfer from the reduced flavoprotein to its electron acceptors, such as cytochrome b5, through a detailed description of the flavin and NADH-binding sites. This information might help to understand better the processes and modifications involved in reactive oxygen formation by the cytochrome b5 reductase. Nevertheless, more than half a century since this enzyme was first purified, the one-electron transfer process toward potential electron acceptors of the reductase is still only partially understood. New advances in computational analysis of protein structures allow predicting the intramolecular protein dynamics, identifying potential functional sites, or evaluating the effects of microenvironment changes in protein structure and dynamics. We applied this approach to characterize further the roles of amino acid domains within cytochrome b5 reductase structure, part of the catalytic domain, and several sensors and structural domains involved in the interactions with cytochrome b5 and other electron acceptors. The computational analysis results allowed us to rationalize some of the available spectroscopic data regarding ligand-induced conformational changes leading to an increase in the flavin adenine dinucleotide (FAD) solvent-exposed surface, which has been previously correlated with the formation of complexes with electron acceptors.

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Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rsupporting

confidence: 66%

Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rmentioning

confidence: 95%

Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rmentioning

confidence: 99%

Section: The Electron Transfer From the Cytochrome B 5 Reductase To Multiple Acceptors And Implication In Rmentioning

confidence: 99%

Section: Intramolecular Dynamics Of C B 5 Rmentioning

confidence: 99%

See 3 more Smart Citations

Structural Features of Cytochrome b5–Cytochrome b5 Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome b5 Reductase

Gutiérrez‐Merino

Martı́nez-Costa

Monsalve

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

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Wielding the double-edged sword: Redox drug delivery systems for inflammatory bowel disease

Chen,

Shui,

Yuan

et al. 2023

Journal of Controlled Release

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Bilirubin Nanomedicines for the Treatment of Reactive Oxygen Species (ROS)-Mediated Diseases

et al. 2020

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Reactive oxygen species (ROS) are chemically reactive species that are produced in cellular aerobic metabolism. They mainly include superoxide anion, hydrogen peroxide, hydroxyl radicals, singlet oxygen, ozone, and nitric oxide and are implicated in many physiological and pathological processes. Bilirubin, a cardinal pigment in the bile, has been increasingly investigated to treat cancer, diabetes, ischemia–reperfusion injury, asthma, and inflammatory bowel diseases (IBD). Indeed, bilirubin has been shown to eliminate ROS production, so it is now considered as a promising therapeutic agent for ROS-mediated diseases and can be used for the development of antioxidative nanomedicines. This review summarizes the current knowledge of the physiological mechanisms of ROS production and its role in pathological changes and focuses on discussing the antioxidative effects of bilirubin and its application in the experimental studies of nanomedicines. Previous studies have shown that bilirubin was mainly used as a responsive molecule in the microenvironment of ROS overproduction in neoplastic tissues for the development of anticancer nanodrugs; however, it could also exert powerful ROS scavenging activity in chronic inflammation and ischemia–reperfusion injury. Therefore, bilirubin, as an inartificial ROS scavenger, is expected to be used for the development of nanomedicines against more diseases due to the universality of ROS involvement in human pathological conditions.

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Human erythrocytes exposure to juglone leads to an increase of superoxide anion production associated with cytochrome b5 reductase uncoupling

Cited by 5 publications

References 62 publications

Structural Features of Cytochrome b5–Cytochrome b5 Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome b5 Reductase

Structural Features of Cytochrome b5–Cytochrome b5 Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome b5 Reductase

Wielding the double-edged sword: Redox drug delivery systems for inflammatory bowel disease

Bilirubin Nanomedicines for the Treatment of Reactive Oxygen Species (ROS)-Mediated Diseases

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