Thioredoxin-interacting
protein (TXNIP), also known as vitamin-D(3) upregulated
protein 1, interacts with reduced
thioredoxin. This
protein modulates the cellular redox state and plays a role in stress-induced cellular apoptosis. This study examined TXNIP gene expression in
prostate cancer cells. In vitro studies by immunoblot assay have shown that elevated
glucose levels (1-15 mM) upregulate TXNIP gene expression two- to fourfold in human prostate
carcinoma cells (LNCaP) and
hepatocellular carcinoma cells (HepG2). Transient gene expression assays reveal that the promoter activity of the TXNIP gene is upregulated by
glucose,
3-O-methylglucose, and
maltose, but not by
mannitol. These results suggest that
glucose and
3-O-methylglucose induce TXNIP expression through both
glucose metabolism-dependent and -independent pathways. Cotransfection of a plasmid expression
carbohydrate response element-
binding protein (ChREBP) with a TXNIP reporter vector into LNCaP cells dramatically enhances reporter activity in a low
glucose (1 mM) condition. The effects of
glucose are apparently mediated in a region located -341 to -324 bp upstream of the translational starting point of the TXNIP gene as indicated by 5'-deletion and site-directed mutagenesis reporter assays. Mutation of the putative
carbohydrate response element (ChoRE) from CACGAGGGCAGCACGAG to TTTGAGGGCAGCACGAG abolishes
glucose upregulation of TXNIP promoter activity. The present study demonstrates that TXNIP is transcription induced in both LNCaP and HepG2 cells in an increased
glucose metabolism-dependent or -independent response, and a putative
glucose regulatory system including ChREBP and ChoRE is needed for
glucose-induced TXNIP gene in human prostate
carcinoma cells.