Activation and up-regulation of nitric oxide synthase in human umbilical vein endothelial cells by polycyclic aromatic hydrocarbons.
PAHs, including naphthalene, fluoranthene and fluorene rapidly induced extracellular Ca(2+) influx and hence elevation of intracellular Ca(2+) concentration and NO production. The effect can be inhibited by Ca(2+) channel blocker but not by P450 inhibitor. In addition to the rapid effect, we have also found that the eNOS mRNA and protein expression were augmented in HUVECs treated with PAHs at concentration as low as 0.1 microM for 24 h. These effects were abolished when the HUVECs were pretreated with the BAPTA, NiCl(2) and SKF96365, as well as SKF525A. Our results revealed that, for the first time, PAHs induce the activation of eNOS and enhance eNOS protein expression in HUVECs both in a Ca(2+)-dependent manner.
Li
Ching-Hao
CH
Institute of Toxicology, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Section 1, Taipei 100, Taiwan, ROC.
Lee
Chen-Chen
CC
Cheng
Yu-Wen
YW
Juang
Hwe-Ann
HA
Kang
Jaw-Jou
JJ
D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D004785:Environmental Pollutants / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D015854:Up-Regulation
D002121:Calcium Channel Blockers; D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D002118:Calcium