Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis

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Rugemalira , E , Roine , I , Kuligowski , J , Sanchez-Illana , A , David Pineiro-Ramos , J , Andersson , S , Peltola , H , Leite Cruzeiro , M , Pelkonen , T & Vento , M 2019 , ' Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis ' , Antioxidants , vol. 8 , no. 10 , 441 . https://doi.org/10.3390/antiox8100441

Title: Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis
Author: Rugemalira, Emilie; Roine, Irmeli; Kuligowski, Julia; Sanchez-Illana, Angel; David Pineiro-Ramos, Jose; Andersson, Sture; Peltola, Heikki; Leite Cruzeiro, Manuel; Pelkonen, Tuula; Vento, Maximo
Contributor: University of Helsinki, Children's Hospital
University of Helsinki, HUS Children and Adolescents
University of Helsinki, HUS Children and Adolescents
University of Helsinki, HUS Children and Adolescents
Date: 2019-10
Language: eng
Number of pages: 11
Belongs to series: Antioxidants
ISSN: 2076-3921
URI: http://hdl.handle.net/10138/309545
Abstract: The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in the cerebrospinal fluid (CSF) of pediatric BM patients. Phenylalanine (Phe), para-tyrosine (p-Tyr), nucleoside 2'-deoxiguanosine (2dG), and biomarkers of ROS/RNS-induced protein and DNA oxidation: ortho-tyrosine (o-Tyr), 3-chlorotyrosine (3Cl-Tyr), 3-nitrotyrosine (3NO(2)-Tyr) and 8-oxo-2'-deoxyguanosine (8OHdG), concentrations were measured by liquid chromatography coupled to tandem mass spectrometry in the initial CSF of 79 children with BM and 10 without BM. All biomarkers, normalized with their corresponding precursors, showed higher median concentrations (p <0.0001) in BM compared with controls, except 8OHdG/2dG. The ratios o-Tyr/Phe, 3Cl-Tyr/p-Tyr and 3NO(2)-Tyr/p-Tyr were 570, 20 and 4.5 times as high, respectively. A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both). In conclusion, biomarkers indicating oxidative damage to proteins distinguished BM patients from non-BM, most clearly the o-Tyr/Phe ratio. The high 3Cl-Tyr/p-Tyr ratio in pneumococcal meningitis suggests robust inflammation because 3Cl-Tyr is a marker of MPO activation and, indirectly, of inflammation.
Subject: oxidative stress
protein damage
myeloperoxidase
bacterial meningitis
developing countries
TYROSINE ISOMERS
STRESS
MARKERS
PATHOPHYSIOLOGY
PATHOGENESIS
OXIDANT
DAMAGE
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
317 Pharmacy
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