[en] Background: Thiamine deficiency (TD) has a number of features in common with the neurodegenerative diseases development and close relationship between TD and oxidative stress (OS) has been repeatedly reported in the literature. The aim of this study is to understand how alimentary TD, accompanied by OS, affects the expression and level of two thiamine metabolism proteins in rat brain, namely, thiamine transporter 1 (THTR1) and thiamine pyrophosphokinase (TPK1), and what factors are responsible for the observed changes.
Methods: The effects of OS caused by TD on the THTR1and TPK1 expression in rat cortex, cerebellum and hippocampus were examined. The levels
of active and oxidized forms of ThDP (enzymatically measured) in the blood and brain, ROS and SH-groups in the brain were also analyzed.
Results: TD increased the expression of THTR1 and protein level in all studied regions. In contrast, expression of TPK1 was depressed. TD-induced OS led to the accumulation of ThDP oxidized inactive form (ThDPox) in the blood and brain. In vitro reduction of ThDPox by dithiothreitol regenerates active ThDP suggesting that ThDPox is in disulfide form. A single high-dose thiamine administration to TD animals had no effect on THTR1 expression, partly raised TPK1 mRNA and protein levels, but is unable to normalize TPK1 enzyme activity. Brain and blood ThDP levels were increased in these conditions, but ThDPox was not decreased.
General significance: It is likely, that the accumulation of ThDPox in tissue could be seen as a potential marker of neurocellular dysfunction and thiamine metabolic state.
Thiamine deficiency in rats affects thiamine metabolism possibly through the formation of oxidized thiamine pyrophosphate
Publication date :
2021
Journal title :
Biochimica et Biophysica Acta - General Subjects
ISSN :
0304-4165
eISSN :
1872-8006
Publisher :
Elsevier, Netherlands
Volume :
1865
Pages :
129980
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FEBS - Fédération des Associations Européennes de Biochimie FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture Palladin Institute of Biochemistry of Ukrainian National Academy of Science F.R.S.-FNRS - Fonds de la Recherche Scientifique
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