Synthetic liver X receptor agonist T0901317 inhibits semicarbazide-sensitive amine oxidase gene expression and activity in apolipoprotein E knockout mice.
Semicarbazide-sensitive amine oxidase (SSAO) catalyzes oxidative deamination of primary aromatic and aliphatic amines. Increased SSAO activity has been found in atherosclerosis and diabetes mellitus. We hypothesize that the anti-atherogenic effect of liver X receptors (LXRs) might be related to the inhibition of SSAO gene expression and its activity. In this study, we investigated the effect of LXR agonist T0901317 on SSAO gene expression and its activity in apolipoprotein E knockout (apoE(-/-)) mice. Male apoE(-/-) mice (8 weeks old) were randomly divided into four groups: basal control group; vehicle group; prevention group; and treatment group. SSAO gene expression was analyzed by real-time quantitative polymerase chain reaction and its activity was determined. The activity of superoxide dismutase and content of malondialdehyde in the aorta and liver were also determined. In T0901317-treated mice, SSAO gene expression was significantly decreased in the aorta, liver, small intestine, and brain. SSAO activities in serum and in these tissues were also inhibited. The amount of superoxide dismutase in the aorta and liver of the prevention group and treatment group was significantly higher compared with the vehicle group (P<0.05). Malondialdehyde in the tissues of these two groups was significantly lower compared with the vehicle group (P<0.05). Our results showed that T0901317 inhibits SSAO gene expression and its activity in atherogenic apoE(-/-) mice. The atheroprotective effect of LXR agonist T0901317 is related to the inhibition of SSAO gene expression and its activity.
Dai
Xiaoyan
X
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, China.
Ou
Xiang
X
Hao
Xinrui
X
Cao
Dongli
D
Tang
Yaling
Y
Hu
Yanwei
Y
Li
Xiaoxu
X
Tang
Chaoke
C
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000008:administration & dosage*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D006631:Amine Oxidase (Copper-Containing); D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse