Dataset Information

Acetaminophen-induced S-nitrosylation and S-sulfenylation signalling in 3D cultured hepatocarcinoma cell spheroids.

ABSTRACT: In this project we have studied human hepatoma cell line grown in 3D spheroids subjected to APAP (acetaminophen) treatment. Global protein expression analysis (label free) and analysis of cysteine oxidations (SNO/SOH TMT proteomics) have been combined to get insights in to the molecular response triggered.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

SUBMITTER: Adelina Rogowska-Wrzesinska

LAB HEAD: Adelina Rogowska-Wrzesinska

PROVIDER: PXD003587 | Pride | 2018-10-18

REPOSITORIES: Pride

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Acetaminophen-induced S-nitrosylation and S-sulfenylation signalling in 3D cultured hepatocarcinoma cell spheroids.

Wojdyla Katarzyna K Wrzesinski Krzysztof K Williamson James J Fey Stephen J SJ Rogowska-Wrzesinska Adelina A

Toxicology research 20160302 3

Acetaminophen (APAP) is possibly the most widely used medication globally and yet little is known of its molecular effects at therapeutic doses. Using a novel approach, we have analysed the redox proteome of the hepatocellular cell line HepG2/C3A treated with therapeutic doses of APAP and quantitated both individual protein abundance and their reversible S-nitrosylation (SNO) and S-sulfenylation (SOH) modifications by mass spectrometry. APAP treatment results in a late, transient i ...[more]

PMID: 30090399

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Project description:Human prion diseases are fatal neurodegenerative disorders characterized by neuronal damage in brain. Protein S-nitrosylation, the covalent adduction of a NO to cysteine, plays a role in human brain biology, and brain dysfunction is a prominent feature of pPrion disease, yet the direct brain targets of S-nitrosylation are largely unknown. We described the first proteomic analysis of global S-nitrosylation in brain tissues of sporadic Creutzfeldt–Jakob disease (sCJD), fatal familial insomnia (FFI) and genetic CJD with a substitution of valine for glycine at codon 114 of the prion protein gene (G114V gCJD) accompanying with normal control with isobaric tags for relative and absolute quantitation (iTRAQ) combined with a nano-HPLC/Q Exactive Mass spectrometry platform. In parallel, we used several approaches to provide quality control for the experimentally defined S-nitrosylated proteins. Total 1509 S-nitrosylated proteins (SNO-proteins) were identified, and cerebellum tissues appeared to contain more commonly differentially expressed SNO-proteins (DESPs) than cortex of sCJD, FFI and gCJD. Three selected SNO-proteins were verified by Western blots, consistent with proteomics assays. Gene ontology analysis showed that more up-regulated DESPs were involved in metabolism, cell cytoskeleton/structure and immune system both in cortex and cerebellum, while more down-regulated ones in both regions were involved in cell cytoskeleton/structure, cell-cell communication and miscelaneous function protein. Pathway analysis suggested that systemic lupus erythematosus, pathogenic Escherichia coli infection, extracellular matrix-receptor interaction were the most commonly affected pathways, which were identified from at least two different diseases. Using STRING database, the network of immune system and cell cytoskeleton and structure were commonly identified in the context of the up-regulated and down-regulated DESPs, respectively, both in cortex and cerebellum. Our study thus have implications for understanding the molecular mechanisms of human prion diseases related to abnormal protein S-nitrosylation and pave the way for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases.

			Action	DRS
	FUS02205_iTMT_1_R1.msf	Msf
	FUS02205_iTMT_1_R1.raw	Raw
	FUS02206_iTMT_2_R1.msf	Msf
	FUS02206_iTMT_2_R1.raw	Raw
	FUS02207_iTMT_3_R1.msf	Msf

Dataset Information

Acetaminophen-induced S-nitrosylation and S-sulfenylation signalling in 3D cultured hepatocarcinoma cell spheroids.

Dataset's files

Publications

Acetaminophen-induced <i>S</i>-nitrosylation and <i>S</i>-sulfenylation signalling in 3D cultured hepatocarcinoma cell spheroids.

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