Thiamine deficiency decreases steady-state transketolase and pyruvate dehydrogenase but not α-ketoglutarate dehydrogenase mRNA levels in three human cell types
Thiamine deficiency decreases steady-state transketolase and pyruvate dehydrogenase but not α-ketoglutarate dehydrogenase mRNA levels in three human cell types
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DOI：
10.1093/jn/128.4.683
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发表时间：
1998-04-01
影响因子：
4.2
通讯作者：
Singleton, CK
中科院分区：
文献类型：
--
作者：
Pekovich, SR;Martin, PR;Singleton, CK
利用硫胺素二磷酸(ThDP)作为辅因子的酶的水平和活性的降低被认为是硫胺素缺乏时造成组织损伤的原因。虽然辅因子的丧失可以部分解释酶活性的丧失，但硫胺素及其磷酸化的衍生物也可能调节编码这些蛋白质的基因的表达。为了验证这种可能性，我们测量了在硫胺素充足和缺乏条件下培养的人成纤维细胞、淋巴母细胞和神经母细胞瘤细胞中三种ThDP依赖酶的稳态信使核糖核酸水平。在硫胺素缺乏培养的三种细胞中，转酮醇酶和丙酮酸脱氢酶复合体的E1β亚基的mRNA水平均较低。相反，α-酮戊二酸脱氢酶的ThDP结合亚基，即E1亚基的mRNA水平没有差异。这些结果表明，硫胺素或硫胺素代谢物可以调节人类体内某些(但不是全部)编码ThDP利用酶的基因的表达。
Reductions in the levels and activities of enzymes that utilize thiamine diphosphate (ThDP) as a cofactor are thought to be responsible for the tissue damage suffered during thiamine deficiency. Although loss of cofactor can account in part for loss of enzyme activity, thiamine and its phosphorylated derivatives may also regulate the expression of the genes encoding these proteins. To examine this possibility, steady-state mRNA levels for three ThDP-dependent enzymes were measured in human fibroblasts, lymphoblasts and neuroblastoma cells cultured under conditions of thiamine sufficiency and deficiency. In all three cell types, the mRNA levels of transketolase and the E1 beta subunit of pyruvate dehydrogenase complex were lower in thiamine-deficient cultures. In contrast, mRNA levels for a ThDP-binding subunit of alpha-ketoglutarate dehydrogenase, the E1 subunit did not differ. These results indicate that thiamine or a thiamine metabolite regulates the expression in humans of some, but not all, genes encoding ThDP-utilizing enzymes.