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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.

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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.

Conflict of interest

The authors have no conflict of interest.

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Correspondence to Dangheng Wei.

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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

Keywords

  • Plasma lipids
  • Lipoproteins
  • Atherosclerosis
  • Physiology
  • Oxidized Lipids