Sheu K F, Calingasan N Y, Dienel G A, Baker H, Jung E H, Kim K S, Paoletti F, Gibson G E
Cornell University Medical college at Burke Medical Research Institute, White Plains, New York 10605, USA.
J Neurochem. 1996 Aug;67(2):684-91. doi: 10.1046/j.1471-4159.1996.67020684.x.
Thiamine deficiency impairs oxidative metabolism and causes metabolic encephalopathy. An early reduction in transketolase (TK) activity may be an important pathogenic event. To assess the role of TK, we have delineated the regional/cellular distribution of TK protein and mRNA in adult rat brain in pyrithiamine-induced thiamine deficiency. TK activity declined in both vulnerable and spared regions. Immunoblots showed a parallel reduction of TK protein. With a few exceptions, immunocytochemistry indicated an overall decline of TK immunoreactivity and the decrease was not specific to vulnerable areas. In contrast to the pronounced, general decline of TK protein, in situ hybridization revealed a regional decrease of 0-25% of TK mRNA in thiamine deficiency. Northern blots indicated a similar level of TK mRNA in whole brain in thiamine deficiency. These results show that the decline of TK activity results from a proportional decrease of TK protein, and the deficiency may be due to an instability of TK protein or an inhibition of TK mRNA translation. The lack of correlation of the distribution, and the absence of specific alteration, of TK in affected regions suggest that the reduced TK may not be linked directly to selective vulnerability in thiamine deficiency.
硫胺素缺乏会损害氧化代谢并导致代谢性脑病。转酮醇酶（TK）活性的早期降低可能是一个重要的致病事件。为了评估TK的作用，我们在吡硫胺诱导的硫胺素缺乏成年大鼠脑中描绘了TK蛋白和mRNA的区域/细胞分布。在易损区域和未受影响区域，TK活性均下降。免疫印迹显示TK蛋白平行减少。除少数例外，免疫细胞化学表明TK免疫反应性总体下降，且这种下降并非易损区域所特有。与TK蛋白明显的普遍下降相反，原位杂交显示硫胺素缺乏时TK mRNA区域减少0 - 25%。Northern印迹表明硫胺素缺乏时全脑中TK mRNA水平相似。这些结果表明，TK活性的下降是由于TK蛋白成比例减少，这种缺乏可能是由于TK蛋白的不稳定性或TK mRNA翻译的抑制。受影响区域中TK分布缺乏相关性且无特异性改变，这表明TK降低可能与硫胺素缺乏时的选择性易损性没有直接联系。
