Gene expression induced by BO-653, probucol and BHQ in human endothelial cells.
2, 3-Dihydro-5-hydroxy-2, 2-dipentyl-4, 6-di-tert-butylbenzofuran (BO-653) and probucol, which act as radical scavenging antioxidants, were developed as anti-atherosclerotic medicines. In order to investigate the effect of these antioxidants on cell functions, we analyzed their ability to regulate gene expression in cultured human umbilical vein endothelial cells (HUVECs) using an oligonucleotide chip. Among 6,416 genes, 17 genes including those encoding mitochondrial proteins and proteins related to oxidative stress response were induced more than 3 fold by BO-653, probucol and tert-butylated hydroquinone (BHO). On the other hand, genes of three subunits of proteasome (PSMA2, PSMA3, PSMA4) were down-regulated by these antioxidants. A gene of cytochrome P-450 1A1 isozyme, a drug-metabolizing phase I enzyme, was expressed only by BHQ treatment. These results suggested that anti-atherogenic antioxidants affected gene expression in HUVECs by which they might regulate cell functions against oxidative stress.
Takabe
W
W
Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro, Japan.
Mataki
C
C
Wada
Y
Y
Ishii
M
M
Izumi
A
A
Aburatani
H
H
Hamakubo
T
T
Niki
E
E
Kodama
T
T
Noguchi
N
N
D000975:Antioxidants / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D001572:Benzofurans / Q000494:pharmacology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D011341:Probucol / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000975:Antioxidants; D001572:Benzofurans; D006873:Hydroquinones; D009097:Multienzyme Complexes; D012333:RNA, Messenger; C018855:2-tert-butylhydroquinone; D019363:Cytochrome P-450 CYP1A1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D011341:Probucol