Expression of E16/CD98LC/hLAT1 is responsive to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
We employed cDNA representational difference analysis to identify new genes that are upregulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a human hepatoblastoma cell line HepG2. We isolated several TCDD-responsive cDNAs. Sequence analysis revealed that one of them encodes E16/CD98LC/hLAT1, an integral membrane protein involved in multiple cellular functions including cellular transport of L-type amino acids. Northern blot analysis confirmed the TCDD-dependent upregulation of the mRNA. Induction of E16/CD98LC/hLAT1 mRNA by TCDD did not require de novo protein synthesis as revealed by the experiment using cycloheximide. Consistent with the changes at mRNA level, the transport of 3H-leucine into HepG2 cells was significantly increased by TCDD treatment. These findings provide a novel aspect of biological effects of TCDD on human hepatocytes.
Sarkar
D
D
Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Japan.
Kambe
F
F
Hirata
A
A
Iseki
A
A
Ohmori
S
S
Seo
H
H
D026905:Amino Acid Transport Systems; D015703:Antigens, CD / Q000096:biosynthesis*; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D027261:Fusion Regulatory Protein-1; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1; D007930:Leucine / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013723:Teratogens / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D026905:Amino Acid Transport Systems; D015703:Antigens, CD; D002352:Carrier Proteins; D018076:DNA, Complementary; D027261:Fusion Regulatory Protein-1; D027283:Large Neutral Amino Acid-Transporter 1; D008565:Membrane Proteins; D000072317:Polychlorinated Dibenzodioxins; D011500:Protein Synthesis Inhibitors; D013723:Teratogens; D003513:Cycloheximide; D007930:Leucine