Thiamine deficiency decreases steady-state transketolase and pyruvate dehydrogenase but not alpha-ketoglutarate dehydrogenase mRNA levels in three human cell types.
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 E1beta 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.
Pekovich
S R
SR
Department of Molecular Biology, Vanderbilt University, Nashville, TN 37235, USA.
Martin
P R
PR
Singleton
C K
CK
D015152:Blotting, Northern; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D013832:Thiamine Deficiency / Q000378:metabolism*; D014158:Transcription, Genetic; D014174:Transketolase / Q000235:genetics*
D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; D007655:Ketoglutarate Dehydrogenase Complex; D014174:Transketolase