title: Oxidized low-density lipoprotein inhibits THP-1-derived macrophage autophagy via TET2 down-regulation.
abstract: Oxidized low-density lipoprotein (ox-LDL) is an independent risk factor of atherosclerosis. However, the mechanism underlying its pro-atherosclerosis roles has not yet been well explored. DNA demethylation modification, via DNA methyltransferases or ten-eleven-translocation (TET) family, is a crisis epigenetic regulation for various biological and pathological processes. This study aimed to investigate the effects of ox-LDL on macrophage autophagy and its potential epigenetic mechanism. Results showed that after treatment with 0, 10, 20, 40 or 80 mg/L ox-LDL for 24 h, the autophagy markers Beclin 1 and LC3 expression were obviously decreased at protein levels (P < 0.05). The mRNA and protein expression of TET2 was evidently decreased (P < 0.05). After pre-treatment with TET2 siRNA, the mRNA and protein levels of Beclin 1 and LC3 decreased compared with the 80 mg/L treatment group (P < 0.01). The mRNA and protein levels of Beclin 1 and LC3-II were up-regulated (P < 0.05) in the 5-aza-2'-deoxycytidine (a DNA methyltransferase inhibitor) of pretreatment group. Consistent with the Western blot results, cell immunofluorescence showed that the protein concentration of LC3-II decreased in the TET2 siRNA group and increased in the 5-aza-2'-deoxycytidine group. Taken together, these results showed that DNA demethylation modifications regulate ox-LDL-treated THP-1 macrophages autophagy and TET2 might be a novel regulator.
authors.affiliation: Key Laboratory for Arteriosclerology of Hunan Province, The Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Li
authors.forename: Zhihan
authors.initials: Z
authors.lastname: Tang
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Jiang
authors.forename: Dangheng
authors.initials: D
authors.lastname: Wei
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy; D000071186:Beclin-1; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D004268:DNA-Binding Proteins; D008077:Lipoproteins, LDL; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C099252:oxidized low density lipoprotein; D049308:Dioxygenases; C541081:TET2 protein, human