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 (ThDP_ox) in the blood and brain. In vitro reduction of ThDP_ox by dithiothreitol regenerates active ThDP suggesting that ThDP_ox 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_ox was not decreased.

General significance

It is likely, that the accumulation of ThDP_ox in tissue could be seen as a potential marker of neurocellular dysfunction and thiamine metabolic state.

中文翻译：

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大鼠硫胺素缺乏可能通过氧化硫胺素焦磷酸的形成影响硫胺素代谢

背景

硫胺素缺乏症 (TD) 与神经退行性疾病的发展具有许多共同特征，文献中多次报道了硫胺素缺乏症 (TD) 与氧化应激 (OS) 之间的密切关系。本研究的目的是了解伴随 OS 的消化性 TD 如何影响大鼠脑中两种硫胺素代谢蛋白，即硫胺素转运蛋白 1 (THTR1) 和硫胺素焦磷酸激酶 (TPK1) 的表达和水平，以及哪些因素是负责的对于观察到的变化。

方法

考察TD引起的OS对大鼠皮层、小脑和海马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（酶法测量）、大脑中的 ROS 和 SH 组的水平。

结果

TD 增加了所有研究区域中 THTR1 的表达和蛋白质水平。相比之下，TPK1 的表达受到抑制。TD 诱导的 OS 导致 ThDP 氧化无活性形式 (ThDP _ox ) 在血液和大脑中的积累。通过二硫苏糖醇在体外还原 ThDP _ox再生了活性 ThDP，表明 ThDP _ox处于二硫化物形式。对 TD 动物进行单次高剂量硫胺素给药对 THTR1 表达没有影响，部分提高了 TPK1 mRNA 和蛋白质水平，但无法使 TPK1 酶活性正常化。在这些条件下，大脑和血液中的 ThDP 水平升高，但 ThDP _ox并未降低。

一般意义

ThDP _ox在组织中的积累很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。