Homocysteine-Mediated PPARα,γ DNA Methylation and Its Potential Pathogenic Mechanism in Monocytes

• DOI: 10.1089/dna.2007.0658
• Publication Date: 2007-11-16T00:33:26Z
• Authors: Jiang Yideng; Liu Zhihong; Xiong Jiantuan; Cao Jun; Li Guizhong; Wang Shuren
• Keywords: 0301 basic medicine; S-Adenosylmethionine; Base Sequence; Molecular Sequence Data; DNA Methylation; Macrophage Activation; S-Adenosylhomocysteine; Monocytes; 3. Good health; Enzyme Activation; Lipoproteins, LDL; PPAR gamma; 03 medical and health sciences; Humans; Tetradecanoylphorbol Acetate; PPAR alpha; DNA (Cytosine-5-)-Methyltransferases; RNA, Messenger; Homocysteine; Cells, Cultured; Foam Cells

Homocysteine (Hcy) is an independent risk factor for cardiovascular disease, but the molecular mechanisms causing atherosclerosis in monocytes remain poorly characterized. The objective of present study was to investigate effects Hcy on DNA methylation PPARalpha,gamma and underlying mechanism expression that induced by monocytes. About 50, 100, 200, 500 microM were added cultured 48 h. acted as lipid sensors bind with mM affinities ligands antiatherosclerosis determined real-time reverse transcription-polymerase chain reaction Western blotting Here, we used a high-throughput quantitative assay utilizes fluorescence-based polymerase determine levels methylation. S-adenosylmethionine (SAM) level S-adenosylhomocysteine (SAH) detected high performance liquid chromatography. Results indicated promoter increased comparison control group, peak 100 muM however, dose-dependent increase increasing not seen. also decreased mRNA protein Further, addition Hcy, SAH elevated, SAM ratio SAM/SAH lower, activity C-5MT-ase increased. In conclusion, these results suggest may represent important explain atherosclerosis, which become therapeutic target preventing Hcy.