title: Thioredoxin-interacting protein: an oxidative stress-related gene is upregulated by glucose in human prostate carcinoma cells.
abstract: 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.
authors.affiliation: Division of Urology, Department of Surgery, Chang Gung Memory Hospital, Taiwan, ROC.
authors.forename: See-Tong
authors.initials: ST
authors.lastname: Pang
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsieh
authors.forename: Cheng-Keng
authors.initials: CK
authors.lastname: Chuang
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Chao
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Weng
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D019325:3-O-Methylglucose / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008320:Maltose / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; C486715:TXNIP protein, human; D019325:3-O-Methylglucose; D008320:Maltose; D005947:Glucose