Dataset Information

Redox Proteomics Analysis of Auranofin Exposed Ovarian Cancer Cells

ABSTRACT: The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were explored through a robust investigative strategy based on joint expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, associated metabolic changes with conversion to a glycolytic phenotype, induction of ER stress. The occurrence of the above cellular changes was extensively validated by performing direct biochemical assays. Our data are consistent with the concept that AF produces its effects through a multitarget mechanism that mainly affects the redox metabolism and mitochondrial functions and results in severe ER stress. Results are discussed in the frame of the current mechanistic knowledge existing on AF.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Giovanni Chiappetta

LAB HEAD: Joelle Vinh

PROVIDER: PXD028681 | Pride | 2022-05-19

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 14

Publications

Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780).

Chiappetta Giovanni G Gamberi Tania T Faienza Fiorella F Limaj Xhesika X Rizza Salvatore S Messori Luigi L Filomeni Giuseppe G Modesti Alessandra A Vinh Joelle J

Redox biology 20220322

The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were investigated through a strategy based on simultaneous expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, metabolic changes associated wit ...[more]

PMID: 35358852

Similar Datasets

Project description:Alcohol consumption induces hepatocyte damage through complex processes involving oxidative stress and disrupted metabolism. Combined, these factors alter proteomic and epigenetic marks providing a critical opportunity to identify therapeutic targets. Indeed, alcohol-induced protein acetylation is a key post-translational modification (PTM) that regulates hepatic metabolism and is associated with the pathogenesis of alcohol-associated liver disease (ALD). Interestingly, recent evidence suggests lysine acetylation occurs when a proximal cysteine residue is within ~15 Å of a lysine residue, referred to as a cysteine-lysine (Cys-Lys) pair. Here, acetylation can occur through the transfer of an acetyl moiety via an S à N acetyl transfer reaction. Alcohol-mediated hepatic redox stress is known to occur coincident with lysine acetylation, but the biochemical mechanisms related to cysteine and lysine crosstalk within ALD remain unexplored. A chronic murine model of ALD was employed to quantify hepatic cysteine redox and lysine acetylation, revealing that alcohol metabolism significantly reduced the cysteine proteome and increased protein acetylation. Interrogating both cysteine redox and lysine acetylation datasets, 1,281 proteins were mapped by AlphaFold2 to quantify distances between 557,815 cysteine and lysine residues. This process identified 388,698 Cys-Lys pairs that were further used to evaluate thiol redox signaling. Our analysis reveals that alcohol metabolism induces redox changes and acetylation selectively on proximal Cys-Lys pairs with an odds ratio of 1.89 (p< 0.0001). We also identified key redox signaling hubs embedded in metabolic pathways associated with ALD, including lipid metabolism, the TCA cycle, and the electron transport chain. Specific protein targets embedded across these pathways include Echs1, Glrx5, Decr2, and Adh1, among many others. Interestingly, these proximal Cys-Lys exist as four major protein motifs represented by the number of Cys and Lys residues that are pairing (Cysx-Lysx). These motifs include Cys1:Lys1, Cysx:Lys1, Cys1:Lysx and Cysx:Lysx each with a unique microenvironment likely indicative of the mode of enzymatic regulation occurring. The motifs are composed of functionally relevant amino acids altered within ALD, identifying sites of therapeutic potential. Furthermore, these unique Cys-Lys redox signatures are translationally relevant as revealed by orthologous comparison with severe alcohol-associated hepatitis (SAH) explants, revealing numerous pathogenic thiol redox signals in these patients.

			Action	DRS
	Set_of_2_files-_3_.msf	Msf
	Set_of_2_files-_3_.pep.xml	Pepxml
	bound_auranofin_1.raw	Raw
	bound_auranofin_2.raw	Raw
	bound_auranofin_3.raw	Raw