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.
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Abbreviations
- ox-LDL:
-
Oxidized low-density lipoprotein
- ATG5:
-
Autophagy-related gene 5
- 5hmC:
-
5-Hydroxymethylcytosine
- TET:
-
Ten-eleven translocation
- Azad:
-
5-Aza-2′-deoxycytidine
- BSA:
-
Bovine serum albumin
- LC3:
-
Microtubule-associated protein 1 light chain 3
- PMA:
-
Phorbol-12-myristate-13-acetate
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Acknowledgments
This research program was supported by grants from the National Natural Science Foundation of China (81370378) and the construct program of the key discipline in the Hunan province.
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Li, G., Peng, J., Liu, Y. et al. Oxidized Low-Density Lipoprotein Inhibits THP-1-Derived Macrophage Autophagy via TET2 Down-regulation. Lipids 50, 177–183 (2015). https://doi.org/10.1007/s11745-014-3977-5
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DOI: https://doi.org/10.1007/s11745-014-3977-5