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Title: Transketolase and vitamin B1 influence on ROS-dependent neutrophil extracellular traps (NETs) formation
Authors: Donporn Riyapa
Darawan Rinchai
Veerachat Muangsombut
Chayanin Wuttinontananchai
Mohammed Toufiq
Damien Chaussabel
Manabu Ato
Jenefer M. Blackwell
Sunee Korbsrisate
University of Cambridge
National Institute of Infectious Diseases
Mahidol University
Faculty of Medicine, Siriraj Hospital, Mahidol University
Telethon Kids Institute
Systems Biology and Immunology Department
Sidra Medicine
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2019
Citation: PLoS ONE. Vol.14, No.8 (2019)
Abstract: © 2019 Riyapa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Neutrophil extracellular traps (NETs) are a recently identified, web-like, extracellular structure composed of decondensed nuclear DNA and associated antimicrobial granules. NETs are extruded into the extracellular environment via the reactive oxygen species (ROS)-dependent cell death pathway participating in inflammation and autoimmune diseases. Transketolase (TKT) is a thiamine pyrophosphate (vitamin B1)-dependent enzyme that links the pentose phosphate pathway with the glycolytic pathway by feeding excess sugar phosphates into the main carbohydrate metabolic pathways to generate biosynthetic reducing capacity in the form of NADPH as a substrate for ROS generation. In this work, TKT was selected as a lead candidate from 24 NET-associated proteins obtained by literature screening and knowledge gap assessment. Consequently, we determined whether TKT influenced NET formation in vitro. We firstly established that the release of ROS-dependent NETs was significantly decreased after purified human PMNs were pretreated with oxythiamine, a TKT inhibitor, and in a concentration dependent manner. As a cofactor for TKT reaction, we evaluated the release of NET formation either in vitamin B1 treatment or in combined use of oxythiamine and vitamin B1, and found that those treatments also exerted a significant suppressive effect on the amount of NET-DNA and ROS production. The regulation of TKT by oxythiamine and/ or vitamin B1 may therefore be associated with response to the modulation of NET formation by preventing generation of excessive NETs in inflammatory diseases.
ISSN: 19326203
Appears in Collections:Scopus 2019

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