Elevated nucleosome levels in systemic inflammation and sepsis*

Zeerleder, Sacha; Zwart, Bas; Wuillemin, Walter A.; Aarden, Lucien A.; Groeneveld, A. B. Johan; Caliezi, Christoph; Nieuwenhuijze, Annemarie van; Mierlo, Gerard J. van; Eerenberg, A. J. M.; Lämmle, Bernhard; Hack, C. E.

doi:10.1097/01.ccm.0000074719.40109.95

Cited by 216 publications

(236 citation statements)

References 24 publications

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“…Elevated levels of nucleosomes in serum resulting from cell necrosis during sepsis have been described and strongly correlate with the severity of sepsis (39). Finally, oxidation of Met-361 in the NADP-dependent malic enzyme was the only oxidation event that was identified in both experiments.…”

Section: A Cofradic Methods For Isolating Peptides Containingmentioning

confidence: 67%

Redox Proteomics of Protein-bound Methionine Oxidation

Ghesquière

Jonckheere

Colaert

et al. 2011

Molecular & Cellular Proteomics

128

160

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We here present a new method to measure the degree of protein-bound methionine sulfoxide formation at a proteome-wide scale. In human Jurkat cells that were stressed with hydrogen peroxide, over 2000 oxidationsensitive methionines in more than 1600 different proteins were mapped and their extent of oxidation was quantified. Meta-analysis of the sequences surrounding the oxidized methionine residues revealed a high preference for neighboring polar residues. Using synthetic methionine sulfoxide containing peptides designed according to the observed sequence preferences in the oxidized Jurkat proteome, we discovered that the substrate specificity of the cellular methionine sulfoxide reductases is a major determinant for the steady-state of methionine oxidation. This was supported by a structural modeling of the MsrA catalytic center. Finally, we applied our method onto a serum proteome from a mouse sepsis model and identi- Reactive oxygen species (ROS)1 are involved in a broad range of processes including signal transduction and gene expression (1), receptor activation (2), antimicrobial and cytotoxic actions of immune cells (3), and aging and age-related degenerative diseases (4). Cellular oxidative stress is associated with increased levels of reactive oxygen species and the molecular damages they cause (5). Of interest here is that some reactive oxygen species specifically modify targeted biomolecules, whereas others cause nonspecific damage. Peroxides for instance are generally more selective compared with hydroxyl radicals (6). Major ROS targets are proteins, with oxidation occurring both at the peptide backbone and at amino acid side-chains (6). The major oxidation product of protein-bound methionine is methionine sulfoxide, further oxidation of which can lead to methionine sulfone, albeit to a much lesser extent (7). The (patho)physiological importance of this modification is reflected by the methionine sulfoxide reductases (Msr) that are present in nearly all organisms (8, 9): decreased activity of these enzymes was associated with aging and Alzheimer disease (10), and abnormal dopamine signaling was recently found in the methionine sulfoxide reductase A knockout mouse (11). Oxidation of methionine can lead to loss of enzyme activity as shown for a brain voltagedependent potassium channel (12). Other studies suggest that methionine oxidation prevents methylation (13) or has an effect on phosphorylation on serines and threonines proximate to the oxidized site (14). In this respect, protein kinases are also targeted by methionine oxidation affecting their activity (e.g. (15)). Further, oxidation of surface methionines increases the protein surface hydrophobicity (16) and may perturb native protein folding, and such oxidized proteins further often become targets for degradation by the proteasome (17).Although methionines are utmost susceptible to oxidation by several types of ROS (18), no adequate proteomic methodologies exist to characterize the exact sites of oxidation and quantify the degree of oxidation. ...

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Section: A Cofradic Methods For Isolating Peptides Containingmentioning

confidence: 67%

Redox Proteomics of Protein-bound Methionine Oxidation

Ghesquière

Jonckheere

Colaert

et al. 2011

Molecular & Cellular Proteomics

128

160

View full text Add to dashboard Cite

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“…136 The presence of ring hemorrhages around cerebral microvessels at autopsy, 53 or as part of the retinopathy observed in patients 137 would also be compatible with the occurrence of endothelial cell death. Indeed, the high levels of circulating nucleosomes of both parasite and human origins detected in the plasma of patients with severe falciparum malaria, compared with the much lower levels detected in septic patients, 138 would suggest that cell death in this infection may be more extensive than previously appreciated. The host cell types that are affected and cell death pathways involved remain to be defined.…”

Section: Cell Deathmentioning

confidence: 89%

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Gillrie

2016

Tissue Barriers

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Plasmodial species are protozoan parasites that infect erythrocytes. As such, they are in close contact with microvascular endothelium for most of the life cycle in the mammalian host. The hostparasite interactions of this stage of the infection are responsible for the clinical manifestations of the disease that range from a mild febrile illness to severe and frequently fatal syndromes such as cerebral malaria and multi-organ failure. Plasmodium falciparum, the causative agent of the most severe form of malaria, is particularly predisposed to modulating endothelial function through either direct adhesion to endothelial receptor molecules, or by releasing potent host and parasite products that can stimulate endothelial activation and/or disrupt barrier function. In this review, we provide a critical analysis of the current clinical and laboratory evidence for endothelial dysfunction during severe P. falciparum malaria. Future investigations using state-of-the-art technologies such as mass cytometry and organs-on-chips to further delineate parasite-endothelial cell interactions are also discussed.

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“…Recently, extracellular host DNA has gained increased attention as an important DAMP involved in the pathogenesis of multiple diseases. Systemic inflammation and sepsis result in a dramatic increase in circulating extracellular host DNA (11)(12)(13). Immune cells can detect DNA by several sensors in the cytoplasm (14,15).…”

mentioning

confidence: 99%