Synthetic liver X receptor agonist T0901317 inhibits semicarbazide‐sensitive amine oxidase gene expression and activity in apolipoprotein E knockout mice

• Published in: Acta biochimica et biophysica Sinica Vol. 40; no. 3; pp. 261 - 268
• Main Authors: Dai, Xiaoyan, Ou, Xiang, Hao, Xinrui, Cao, Dongli, Tang, Yaling, Hu, Yanwei, Li, Xiaoxu, Tang, Chaoke
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2008
• Subjects: Amine Oxidase (Copper-Containing) - antagonists & inhibitors; Amine Oxidase (Copper-Containing) - metabolism; Animals; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; atherosclerosis; Atherosclerosis - metabolism; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - metabolism; DNA-Binding Proteins - antagonists & inhibitors; Enzyme Activation - drug effects; Gene Expression Regulation, Enzymologic - drug effects; Hydrocarbons, Fluorinated; liver X receptor; Liver X Receptors; Male; Mice; Mice, Knockout; nuclear receptor; Orphan Nuclear Receptors; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; semicarbazide‐sensitive amine oxidase; Sulfonamides - administration & dosage; T0901317
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1111/j.1745-7270.2008.00391.x

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 LXRagonist 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.