title: Vitamin C down-regulate apo(a) expression via Tet2-dependent DNA demethylation in HepG2 cells.
abstract: Lipoprotein(a)[Lp(a)] is a risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Vitamin C is responsible for maintaining the catalytic activity of a group of iron and 2-oxoglutarate (2OG)-dependent dioxygenases and induces the generation of 5-hydroxymethylcytosine (5hmC) via Ten-eleven translocation (Tet) dioxygenases. In addition, It has been reported vitamin C deficiency induces atherosclerosis and increases Lp(a) and apo(a) plasma levels in Lp(a)+ mice. However, the mechanism is still unclear. In this study, we investigated the effects of vitamin C on apo(a) expression and the possible molecular mechanism of vitamin C that influences apolipoprotein(a) [apo(a)] biosynthesis in HepG2 cells. Results showed that vitamin C significantly inhibited the expression and secretion levels of apo(a). Vitamin C can also increase ELK1 expression and hydroxymethylation of ELK1 promoter and the globle DNA in HepG2 cells. In addition, the effects of vitamin C inhibiting the apo(a) expression were attenuated by ELK1siRNA and Tet2siRNA. These results suggested vitamin C down-regulate apo(a) expression via Tet2-dependent DNA demethylation in HepG2 cells.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
authors.forename: Kai
authors.initials: K
authors.lastname: Qu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Ma
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
authors.forename: Ya-Mi
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China; The Second Hospital Affiliated to University of South China, Hengyang 421001, Hunan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: The Second Hospital Affiliated to University of South China, Hengyang 421001, Hunan, China.
authors.forename: Jun-Fa
authors.initials: JF
authors.lastname: Zeng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Lei
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
authors.forename: Dang-Heng
authors.initials: DH
authors.lastname: Wei
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China. Electronic address: smt121101@163.com.
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D053241:Apoprotein(a) / Q000096:biosynthesis / Q000235:genetics*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D019175:DNA Methylation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D049308:Dioxygenases; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007501:Iron / Q000097:blood; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D050807:ets-Domain Protein Elk-1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; D011518:Proto-Oncogene Proteins; D050807:ets-Domain Protein Elk-1; D007501:Iron; D049308:Dioxygenases; C551914:Tet2 protein, mouse; D053241:Apoprotein(a); D001205:Ascorbic Acid
keywords: Apolipoprotein a; Coronary heart diseases; Demethylation; Tet2; Vitamin C