Polychlorinated biphenyls alter the expression of endothelial nitric oxide synthase mRNA in human umbilical vein endothelial cells.
Polychlorinated biphenyls (PCBs) are a group of persistent pollutants that are detected in maternal serum and umbilical cord, suggesting that fetal exposure also needs to be considered. The effects of dioxin-like PCB congeners 3,3',4,4'-tetrachlorobiphenyl (PCB77) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) and a non-dioxin-like compound 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) on the expression of endothelial nitric oxide synthase (eNOS), known to maintain blood flow to the fetus, in human umbilical vein endothelial cells (HUVECs) were investigated. The mRNA levels of eNOS, aryl hydrocarbon receptor (AhR) and cytochrome P450 (CYP) 1A1 in cells treated with 5 microM PCBs for 24 hours were analysed by real-time RT-PCR. Cells were also treated with alpha-naphthoflavone (alpha NF), an AhR antagonist or ICI 182780, an estrogen receptor (ER) antagonist, one hour prior to PCB exposure, to observe the effects of these receptors on eNOS modulation. Each PCB increased the eNOS mRNA level by 4.5-fold that was markedly inhibited by alphaNF. ERs were also suspected of altering eNOS levels because ICI 182780 treatment resulted in a decrease in the eNOS level. These results suggest that the eNOS mRNA expression increases due to the action of PCBs related to both AhR and ERs in HUVECs, and that maternal PCB exposure could influence fetal circulation.
Omori
Naoko
N
Department of Plastic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Fukata
Hideki
H
Sato
Koji
K
Yamazaki
Koji
K
Aida-Yasuoka
Keiko
K
Takigami
Hidetaka
H
Kuriyama
Motone
M
Ichinose
Masaharu
M
Mori
Chisato
C
D001571:Benzoflavones / Q000494:pharmacology; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis*; D011950:Receptors, Cholinergic / Q000235:genetics; D014471:Umbilical Veins / Q000201:enzymology
D001571:Benzoflavones; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D000077267:Fulvestrant; D004958:Estradiol; C011512:alpha-naphthoflavone; D011078:Polychlorinated Biphenyls; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019363:Cytochrome P-450 CYP1A1