Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y+/hCAT-1 and y+/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells.
Intrauterine growth retardation (IUGR) is associated with vascular complications leading to hypoxia and abnormal fetal development. The effect of IUGR on L-arginine transport and nitric oxide (NO) synthesis was investigated in cultures of human umbilical vein endothelial cells (HUVECs). IUGR was associated with membrane depolarization and reduced L-arginine transport (V(max)= 5.8+/-0.2 versus 3.3+/-0.1 pmol/microg protein per minute), with no significant changes in transport affinity (K(m)=159+/-15 versus 137+/-14 micromol/L). L-Arginine transport was trans-stimulated (8- to 9-fold) in cells from normal and IUGR pregnancies. IUGR was associated with reduced production of L-[3H]citrulline from L-[3H] arginine, lower nitrite and intracellular L-arginine, L-citrulline, and cGMP. IUGR decreased hCAT-1 and hCAT-2B mRNA, and increased eNOS mRNA and protein levels. IUGR-associated inhibition of L-arginine transport and NO synthesis, and membrane depolarization were reversed by the NO donor S-nitroso-N-acetyl-L,D-penicillamine. In summary, endothelium from fetuses with IUGR exhibit altered L-arginine transport and NO synthesis (L-arginine/NO pathway), reduced expression and activity of hCAT-1 and hCAT-2B and reduced eNOS activity. Alterations in L-arginine/NO pathway could be critical for the physiological processes involved in the etiology of IUGR in human pregnancies.
Casanello
Paola
P
Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Concepcion, Chile.
Sobrevia
Luis
L
D026923:Amino Acid Transport Systems, Basic; D001120:Arginine / Q000032:analysis / Q000097:blood / Q000378:metabolism; D001692:Biological Transport; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002956:Citrulline / Q000032:analysis / Q000097:blood; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D008564:Membrane Potentials; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D014471:Umbilical Veins / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*
D026923:Amino Acid Transport Systems, Basic; D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D012333:RNA, Messenger; C420825:SLC7A1 protein, human; C414177:SLC7A2 protein, human; D002956:Citrulline; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D008239:Lysine; D005033:Ethylmaleimide