geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Novel intra- and inter-molecular sulfinamide bonds in S100A8 produced by hypochlorite oxidation


, : Novel intra- and inter-molecular sulfinamide bonds in S100A8 produced by hypochlorite oxidation. Journal of Biological Chemistry 276(36): 33393-33401

Hypochlorite is a major oxidant generated when neutrophils and macrophages are activated at inflammatory sites, such as in atherosclerotic lesions. Murine S100A8 (A8) is a major cytoplasmic protein in neutrophils and is secreted by macrophages in response to inflammatory stimuli. After incubation with reagent HOCl for 10 min, approximately 85% of A8 was converted to 4 oxidation products, with electrospay ionization mass spectrometry masses of m/z 10354, 10388, 10354 +/- 1, and 20707 +/- 3. All were resistant to reduction by dithiothreitol. Initial formation of a reactive Cys sulfenic acid intermediate was demonstrated by the rapid conjugation of 5,5-dimethyl-1,3-cyclohexanedione (dimedone) to HOCl-treated A8 to form stable adducts. Matrix-assisted laser desorption-reflectron time of flight peptide mass fingerprinting of isolated oxidation products confirmed the mass additions observed in the full-length proteins. Both Met(36/73) were converted to Met(36/73) sulfoxides. An additional product with an unusual mass addition of m/z 14 (+/-0.2) was identified and corresponded to the addition of oxygen to Cys(41), conjugation to various epsilon-amines of Lys(6), Lys(34/35), or Lys(87) with loss of dihydrogen and formation of stable intra- or inter-molecular sulfinamide cross-links. Specific fragmentations identified in matrix-assisted laser desorption-post source decay spectra and low energy collisional-induced dissociation tandem mass spectroscopy spectra of sulfinamide-containing digest peptides confirmed Lys(34/35) to Cys(41) sulfinamide bonds. HOCl oxidation of mutants lacking Cys(41) (Ala(41)S100A8) or specific Lys residues (e.g. Lys(34/35), Ala(34/35)S100A8) did not form sulfinamide cross-links. HOCl generated by myeloperoxidase and H(2)O(2) and by phorbol 12-myristate 13-acetate-activated neutrophils also formed these products(.) In contrast to the disulfide-linked dimer, oxidized monomer retained normal chemotactic activity for neutrophils. Sulfinamide bond formation represents a novel oxidative cross-linking process between thiols and amines and may be a general consequence of HOCl protein oxidation in inflammation not identified previously. Similar modifications in other proteins could potentially regulate normal and pathological processes during aging, atherogenesis, fibrosis, and neurogenerative diseases.

US$19.90

PMID: 11445563

DOI: 10.1074/jbc.M101566200


Other references

Hawley, E.R.; Piao, H.; Scott, N.M.; Malfatti, S.; Pagani, I.; Huntemann, M.; Chen, A.; Glavina Del Rio, T.; Foster, B.; Copeland, A.; Jansson, J.; Pati, A.; Tringe, S.; Gilbert, J.A.; Lorenson, T.D.; Hess, M., 2014: Metagenomic analysis of microbial consortium from natural crude oil that seeps into the marine ecosystem offshore Southern California. Crude oils can be major contaminants of the marine ecosystem and microorganisms play a significant role in the degradation of its main constituents. To increase our understanding of the microbial hydrocarbon degradation process in the marine ecosy...

Dirksen, K.M.; Hynds, J.A.; Bhavsar, A.R.; Brown-Saltzman, K., 2013: The existential question in palliative sedation: reply to Putman et al. Journal of Pain and Symptom Management 45(5): E1-E2

Ballenger, J.C.; Fyer, A.J., 1993: Examining criteria for panic disorder. Hospital & Community Psychiatry 44(3): 226-228

Qian, J-hong.; Zhu, J-xing.; Zhu, X-dong.; Chen, T-xin., 2010: Clinical features and follow-up of Chinese patients with symptomatic hypogammaglobulinemia in infancy. Hypogammaglobulinemia is common in infant humoral immunodeficiencies and has complicated causes and outcomes. We aimed to determine the clinical manifestations, immunological changes and outcomes of Shanghai infants with hypogammaglobulinemia. Pat...

Fragoso, Y.Dadalti.; Carvalho, R.; Ferrero, F.; Lourenço, D.Maria.; Paulino, E.Regina., 2003: Crying as a precipitating factor for migraine and tension-type headache. Scarcely reported in the literature, crying seems to be an important precipitating factor for both migraine and tension-type headache in daily practice. To evaluate the role of crying as a precipitating factor for migraine and tension-type headach...

Yanagisawa, K.; Tago, K.; Hayakawa, M.; Ohki, M.; Iwahana, H.; Tominaga, S-Ichi., 2002: A novel splice variant of mouse interleukin-1-receptor-associated kinase-1 (IRAK-1) activates nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK). Interleukin-1 (IL-1)-receptor-associated kinase (IRAK) is an indispensable signalling molecule for host-defence responses initiated by a variety of ligands that bind to members of the Toll/IL-1 receptor family. Here we report a novel splice varian...

Tian, C.; Goldstein, S.; Fry, E.S., 2008: On the etalon effect generated by a Pockels cell with high-quality antireflection coatings. We discuss the modulation in the spectrum generated by the windows of a Pockels cell. Although they are antireflection coated, the residual reflectivity of the highly parallel window faces can still have etalon effects that lead to pronounced spec...

Martin, P., 2012: CD44, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1: biomarkers in search of validation in lymphomas. Leukemia & Lymphoma 53(1): 1-2

Gealt M.A., 1988: Recombinant dna plasmid transmission to indigenous organisms during waste treatment. Water Science & Technology 20(11-12): 179-184

Hartman, R.Gay., 2004: AIDS and adolescents. Journal of Health Care Law & Policy 7(2): 280-315