Selective induction of a cationic amino acid transporter by tumor necrosis factor-alpha in vascular endothelium.
Treatment of bovine aortic endothelial cells with tumor necrosis factor-alpha (TNF-alpha) resulted in a concentration-dependent increase in L-arginine transport. The stimulatory effect of TNF-alpha was time-dependent, requiring at least 6 hr of exposure. Both actinomycin D and cycloheximide inhibited the TNF-alpha mediated increase in L-arginine transport, indicating that de novo RNA and protein synthesis were required. Ribonuclease protection analysis revealed the presence of cationic amino acid transporter (CAT)-1 and CAT-2 mRNA. Treatment of bovine aortic endothelial cells with TNF-alpha selectively increased the levels of CAT-2 mRNA, whereas message for CAT-1 remained unchanged. These results demonstrate that TNF-alpha stimulates L-arginine transport in endothelial cells by selectively inducing the expression of CAT-2 mRNA. The capacity of TNF-alpha to stimulate the expression of CAT-2 protein may provide an important mechanism by which increases in substrate are provided to endothelial cells during periods of elevated L-arginine metabolism.
Houston VA Medical Center, TX 77030, USA.
W
W
Durante
L
L
Liao
K
K
Cheng
A I
AI
Schafer
D000818:Animals; D001011:Aorta / Q000166:cytology; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002417:Cattle; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011991:Receptors, Virus; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; C070506:ecotropic murine leukemia virus receptor; D003609:Dactinomycin; D001120:Arginine; D003513:Cycloheximide