Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, 4000 Liège, Belgium.
Biochim Biophys Acta Gen Subj. 2021 Nov;1865(11):129980. doi: 10.1016/j.bbagen.2021.129980. Epub 2021 Aug 12.
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.
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.
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 (ThDP) in the blood and brain. In vitro reduction of ThDP by dithiothreitol regenerates active ThDP suggesting that ThDP 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 ThDP was not decreased.
It is likely, that the accumulation of ThDP in tissue could be seen as a potential marker of neurocellular dysfunction and thiamine metabolic state.
硫胺素缺乏（TD）在许多方面与神经退行性疾病的发展具有共同特征，并且文献中反复报道 TD 与氧化应激（OS）之间存在密切关系。本研究的目的是了解伴随 OS 的饮食性 TD 如何影响两种大鼠脑内硫胺素代谢蛋白的表达和水平，即硫胺素转运蛋白 1（THTR1）和硫胺素焦磷酸激酶（TPK1），以及是什么因素导致了观察到的变化。
研究了 TD 引起的 OS 对大鼠皮质、小脑和海马中 THTR1 和 TPK1 表达的影响。还分析了血液和大脑中活性和氧化形式的 ThDP（酶法测定）、大脑中的 ROS 和 SH 基团的水平。
TD 增加了所有研究区域的 THTR1 和蛋白水平的表达。相比之下，TPK1 的表达受到抑制。TD 诱导的 OS 导致血液和大脑中 ThDP 氧化失活形式（ThDP）的积累。二硫苏糖醇（DTT）体外还原可使活性 ThDP 再生，表明 ThDP 处于二硫键形式。单次大剂量硫胺素给予 TD 动物对 THTR1 表达没有影响，部分提高了 TPK1 mRNA 和蛋白水平，但不能使 TPK1 酶活性正常化。在这些条件下，大脑和血液中的 ThDP 水平增加，但 ThDP 没有减少。
组织中 ThDP 的积累可能被视为神经细胞功能障碍和硫胺素代谢状态的潜在标志物。
