Dataset Information

Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized ?enolase (methionine sulfoxide 93).

ABSTRACT: NETs constitute a network of DNA and proteins released by neutrophils in response to infectious and immunologic triggers. NET proteins are recognized as autoantigens in ANCA vasculitis; limited knowledge is available in other autoimmune pathologies. The composition of NETs produced ex vivo by resting and Phorbol-myristate acetate (PMA) stimulated neutrophils was analyzed by high-throughput Fusion Orbitrap technology in 16 patients with Systemic Lupus Erythematosus/Lupus nephritis (9 SLE/7 LN) and in 11 controls. Seven-hundred proteins were characterized and specific fingerprints discriminated LN from SLE. We focused on methyl-oxidized ?enolase (methionine sulfoxide 93) that was markedly increased in NETs from LN and was localized in NET filaments in tight connection and outlying DNA. The isotype of anti-?enolase antibodies was IgG2 in LN and IgG4 in other autoimmune glomerulonephritis (Membranous Nephropathy, MN); serum anti-?enolase IgG2 were higher in LN than in SLE and absent in MN. The same IgG2 antibodies recognized 5 epitopes of the protein one containing methionine sulphoxide 93. In conclusion, specific NET protein fingerprints characterize different subsets of SLE; methyl-oxidized ?enolase is over-expressed in LN. Circulating anti-?enolase IgG2 recognize the oxidized epitope and are high in serum of LN patients. Post-translational modified NET proteins contribute to autoimmunity in patients with LN.

SUBMITTER: Bruschi M

PROVIDER: S-EPMC6538718 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized αenolase (methionine sulfoxide 93).

Bruschi Maurizio M Petretto Andrea A Santucci Laura L Vaglio Augusto A Pratesi Federico F Migliorini Paola P Bertelli Roberta R Lavarello Chiara C Bartolucci Martina M Candiano Giovanni G Prunotto Marco M Ghiggeri Gian Marco GM

Scientific reports 20190528 1

NETs constitute a network of DNA and proteins released by neutrophils in response to infectious and immunologic triggers. NET proteins are recognized as autoantigens in ANCA vasculitis; limited knowledge is available in other autoimmune pathologies. The composition of NETs produced ex vivo by resting and Phorbol-myristate acetate (PMA) stimulated neutrophils was analyzed by high-throughput Fusion Orbitrap technology in 16 patients with Systemic Lupus Erythematosus/Lupus nephritis (9 SLE/7 LN) an ...[more]

PMID: 31138830

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Project description:Methionine residues in proteins are susceptible to oxidation by reactive oxygen species, but can be repaired via reduction of the resulting methionine sulfoxides by methionine-S-sulfoxide reductase (MsrA) and methionine-R-sulfoxide reductase (MsrB). However, the identity of all methionine sulfoxide reductases involved, their cellular locations and relative contributions to the overall pathway are poorly understood. Here, we describe a methionine-R-sulfoxide reduction system in mammals, in which two MsrB homologues were previously described. We found that human and mouse genomes possess three MsrB genes and characterized their protein products, designated MsrB1, MsrB2, and MsrB3. MsrB1 (Selenoprotein R) was present in the cytosol and nucleus and exhibited the highest methionine-R-sulfoxide reductase activity because of the presence of selenocysteine (Sec) in its active site. Other mammalian MsrBs contained cysteine in place of Sec and were less catalytically efficient. MsrB2 (CBS-1) resided in mitochondria. It had high affinity for methionine-R-sulfoxide, but was inhibited by higher concentrations of the substrate. The human MsrB3 gene gave rise to two protein forms, MsrB3A and MsrB3B. These were generated by alternative splicing that introduced contrasting N-terminal and C-terminal signals, such that MsrB3A was targeted to the endoplasmic reticulum and MsrB3B to mitochondria. We found that only mitochondrial forms of mammalian MsrBs (MsrB2 and MsrB3B) could compensate for MsrA and MsrB deficiency in yeast. All mammalian MsrBs belonged to a group of zinc-containing proteins. The multiplicity of MsrBs contrasted with the presence of a single mammalian MsrA gene as well as with the occurrence of single MsrA and MsrB genes in yeast, fruit flies, and nematodes. The data suggested that different cellular compartments in mammals maintain a system for repair of oxidized methionine residues and that this function is tuned in enzyme- and stereo-specific manner.

Dataset Information

Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized ?enolase (methionine sulfoxide 93).

Publications

Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized αenolase (methionine sulfoxide 93).

Similar Datasets

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