Sortilin alters lipid efflux from lipid-laden THP-1 macrophage by regulating ABCA1 protein

doi:10.13418/j.issn.1001-165x.2020.05.015

Chinese Journal of Clinical Anatomy ›› 2020, Vol. 38 ›› Issue (5) : 568-573. DOI: 10.13418/j.issn.1001-165x.2020.05.015

ZHONG Li-yuan¹, ZHANG Ming-xin², LV Yun-cheng², TAO Shui-ying², HU Yang², WANG Xi², TANG Zhi-hua², PENG Tian-hong²

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Abstract

Objective　To investigate the effect of Sortilin on protein level of macrophage ABCA1 and intracellular lipid efflux. Methods The protein and mRNA levels of lipid-laden macrophage ABCA1 were detected by western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) respectively; the combination of Sortilin with ABCA1 was detected by co-immunoprecipitation (Co-IP); macrophage cholesterol efflux was measured by liquid scintillation counting. Total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) were determined by high performance liquid chromatography (HPLC). Intracellular lipid droplets were observed by oil red O staining. Results Sortilin overexpression significantly decreased protein level of ABCA1, while Sortilin silence obviously raised cellular level of ABCA1 protein in lipid-laden macrophage. ABCA1 mRNA has no significant change in these three groups. Co-IP assay showed that Sortilin combined with ABCA1 protein. Compared to control group, Sortilin overexpression decreased cholesterol efflux from lipid-laden macrophage, resulting in macrophage cholesterol accumulation and lipid droplet generation. Sortilin silence dramatically enhanced cholesterol efflux and decreased lipid droplet formation. Co-treatment with chloroquine can partially abolish the inhibitory role of Sortilin overexpression in ABCA1 protein and lipid efflux of lipid-laden macrophage.　Conclusions　Sortilin reduces protein level of macrophage ABCA1 and intracellular cholesterol efflux, causes the accumulation of intracellular lipid.

Key words

Sortilin / 　Macrophage / 　ABCA1 / 　Cholesterol efflux

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ZHONG Li-yuan, ZHANG Ming-xin, LV Yun-cheng, TAO Shui-ying, HU Yang, WANG Xi, TANG Zhi-hua, PENG Tian-hong. Sortilin alters lipid efflux from lipid-laden THP-1 macrophage by regulating ABCA1 protein[J]. Chinese Journal of Clinical Anatomy. 2020, 38(5): 568-573 https://doi.org/10.13418/j.issn.1001-165x.2020.05.015

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