Redox proteomics and drug development

D’Alessandro, Angelo; Rinalducci, Sara; Zolla, Lello

doi:10.1016/j.jprot.2011.01.001

Cited by 21 publications

(11 citation statements)

References 201 publications

(269 reference statements)

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“…Proteomic responses were recorded through Label Free Quantification (LFQ) in addition to 2-Dimensional Polyacrylamide gel electrophoresis (2D PAGE) methods. LFQ allows a high-resolution assessment of the proteomic changes in the larvae and is becoming an increasingly important tool in identifying the mode of action in in-vitro mammalian cell models [47,48]. Owing to the similarity between the larval and mammal system, this approach will provide valuable insights into the potential mode of action of the phenazine-functionalised Cu(II) phenanthroline complexes in mammalian models.…”

Section: Introductionmentioning

confidence: 99%

In-vivo evaluation of the response of Galleria mellonella larvae to novel copper(II) phenanthroline-phenazine complexes

Rochford¹,

Molphy

Browne

et al. 2018

Journal of Inorganic Biochemistry

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Herein we report the in-vivo characterisation and metabolic changes in Galleria mellonella larvae to a series of bis-chelate copper(II) phenanthroline-phenazine cationic complexes of [Cu(phen)] (Cu-Phen), [Cu(DPQ)(Phen)] (Cu-DPQ-Phen) and [Cu(DPPZ)(Phen)] (Cu-DPPZ-Phen) (where phen = 1,10-phenanthroline, DPQ = dipyrido[3,2-ƒ:2',3'-h]quinoxaline and DPPZ = dipyrido[3,2-a:2',3'-c]phenazine). Our aim was to investigate the influence of the systematic extension of the ligated phenazine ligand in the G. mellonella model as a first step towards assessing the in-vivo tolerance and mode of action of the complex series with respect to the well-studied oxidative chemical nuclease, Cu-Phen. The Lethal Dose (LD) values were established over dose ranges of 2 - 30 μg at 4-, 24-, 48- and 72 h by mortality assessment, with Cu-Phen eliciting the highest mortality at 4 h (Cu-Phen, 12.62 μg < Cu-DPQ-Phen, 21.53 μg < Cu-DPPZ-Phen, 26.07 μg). At other timepoints, a similar profile was observed as the phenazine π-backbone within the complex scaffold was extended. Assessment of both cellular response and related gene expression demonstrated that the complexes did not initiate an immune response. However, Label-Free Quantification proteomic data indicated the larval response was associated with upregulation of key proteins such as Glutathione S-transferase, purine synthesis and glycolysis/gluconeogenesis (e.g. fructose-bisphosphate aldolase and glyceraldehyde-3-phosphate). Both Cu-Phen and Cu-DPQ-Phen elicited a similar in-vivo response in contrast to Cu-DPPZ-Phen, which displayed a substantial increase in nitrogen detoxification proteins and proteins with calcium binding sites. Overall, the response of G. mellonella larvae exposure to the complex series is dominated by detoxification and metabolic proteome response mechanisms.

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Section: Introductionmentioning

confidence: 99%

In-vivo evaluation of the response of Galleria mellonella larvae to novel copper(II) phenanthroline-phenazine complexes

Rochford¹,

Molphy

Browne

et al. 2018

Journal of Inorganic Biochemistry

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“…In this context, redox proteomics might be pivotal in highlighting the main targets of protein oxidations and the biological pathways involved or compromised by these phenomena. Although the application of proteomics to drug design and development is in its earliest phase, preliminary redox proteomics results help to pave the way for further research in this field (D'Alessandro et al, 2011).…”

Section: Human Diseases and Early Hints From Redox Proteomicsmentioning

confidence: 99%

“…Redox signalling can be relayed through intramolecular or intermolecular disulphide formation (Li et al, 2005). Redox proteomics is an emerging branch of proteomics aimed at detecting and analysing redox-based changes within the proteome in different redox statuses (D'Alessandro et al, 2011). For this reason, several experimental approaches have been developed for the systematic characterisation of thiol proteome.…”

Section: Introductionmentioning

confidence: 99%

Protein Thiol Modification and Thiol Proteomics

Li¹,

Wang²,

Li³

2012

Integrative Proteomics

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“…Increased oxidation evoked by ROS is associated with physiological functions during life. ROS represent a fundamental asset to immune cells in immune system responses against pathogens and also play a physiological role in normal plant cell physiology by triggering specific cascades (D'Alessandro et al, ). Nonetheless, in humans oxidative stress (OS) is thought to be involved in disease onset and progression.…”

Section: Introductionmentioning

confidence: 99%

“…Protein carbonyl groups are generated by direct oxidation of several amino acid side chains (i.e., Lys, Arg, Pro, Thr, His, and others), backbone fragmentation, hydrogen atom abstraction at alpha carbons and Michael addition reactions of His, Lys, and Cys residues with products of lipid peroxidation causing inactivation, crosslinking, or breakdown of proteins (Butterfield & Stadtman, ). The most abundant carbonyls in aged cells are 2‐amino‐adipic semialdehyde (AAS) and gamma‐glutamyl semialdehyde (GGS) (D'Alessandro et al, ). Protein carbonyls are also produced by glycation/glycoxidation of Lys amino groups, forming AGEs (Berlett & Stadtman, ; Stadtman & Berlett, ), and Michael adducts of α, β‐unsaturated aldehydes produced by lipid peroxidation (Sultana, Perluigi, & Allan Butterfield, ).…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry and redox proteomics: Applications in disease

et al. 2013

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Proteomics techniques are continuously being developed to further understanding of biology and disease. Many of the pathways that are relevant to disease mechanisms rely on the identification of post‐translational modifications (PTMs) such as phosphorylation, acetylation, and glycosylation. Much attention has also been focused on oxidative PTMs which include protein carbonyls, protein nitration, and the incorporation of fatty acids and advanced glycation products to amino acid side chains, amongst others. The introduction of these PTMs in the cell can occur due to the attack of reactive oxygen and nitrogen species (ROS and RNS, respectively) on proteins. ROS and RNS can be present as a result of normal metabolic processes as well as external factors such as UV radiation, disease, and environmental toxins. The imbalance of ROS and RNS with antioxidant cellular defenses leads to a state of oxidative stress, which has been implicated in many diseases. Redox proteomics techniques have been used to characterize oxidative PTMs that result as a part of normal cell signaling processes as well as oxidative stress conditions. This review highlights many of the redox proteomics techniques which are currently available for several oxidative PTMs and brings to the reader's attention the application of redox proteomics for understanding disease pathogenesis in neurodegenerative disorders and others such as cancer, kidney, and heart diseases. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 33: 277–301, 2014.

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Redox proteomics and drug development

Cited by 21 publications

References 201 publications

In-vivo evaluation of the response of Galleria mellonella larvae to novel copper(II) phenanthroline-phenazine complexes

In-vivo evaluation of the response of Galleria mellonella larvae to novel copper(II) phenanthroline-phenazine complexes

Protein Thiol Modification and Thiol Proteomics

Mass spectrometry and redox proteomics: Applications in disease

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