期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1864, 期 5, 页码 643-653出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2019.01.005
关键词
Glycome; High-density lipoprotein; Low-density lipoprotein; Sialic acid; Cholesterol efflux; Cholesterol accumulation
资金
- National Institute for Health and Medical Research (INSERM)
- ANR (CARINA project) in Paris, France
- Russian Science Foundation [18-15-00254]
- European Union [733100, 722095, 721815]
- European Structural and Investment Funds IRI grant [KK.01.2.1.01.0003]
- Croatian National Centre of Research Excellence in Personalized Healthcare [KK.01.1.1.01.0010]
- Russian Science Foundation [18-15-00254] Funding Source: Russian Science Foundation
Aims: Human plasma lipoproteins are known to contain various glycan structures whose composition and functional importance are starting to be recognized. We assessed N-glycosylation of human plasma HDL and LDL and the role of their glycomes in cellular cholesterol metabolism. Methods: N-glycomic profiles of native and neuraminidase-treated HDL and LDL were obtained using HILICUHPLC-FLD. Relative abundance of the individual chromatographic peaks was quantitatively expressed as a percentage of total integrated area and N-glycan structures present in each peak were elucidated by MALDI-TOF MS. The capacity of HDL to mediate cellular efflux of cholesterol and the capacity of LDL to induce cellular accumulation of cholesteryl esters were evaluated in THP-1 cells. Results: HILIC-UHPLC-FLD analysis of HDL and LDL N-glycans released by PNGase F resulted in 22 and 18 distinct chromatographic peaks, respectively. The majority of N-glycans present in HDL (similar to 70%) and LDL (similar to 60%) were sialylated with one or two sialic acid residues. The most abundant N-glycan structure in both HDL and LDL was a complex type biantennary N-glycan with one sialic acid (A2G2S1). Relative abundances of several N-glycan structures were dramatically altered by the neuraminidase treatment, which selectively removed sialic acid residues. Native HDL displayed significantly greater efficacy in removing cellular cholesterol from THP-1 cells as compared to desialylated HDL (p < 0.05). Cellular accumulation of cholesteryl esters in THP-1 cells was significantly higher after incubations with desialylated LDL particles as compared to native LDL (p < 0.05). Conclusions: N-glycome of human plasma lipoproteins reveals a high level of diversity, which directly impacts functional properties of the lipoproteins.
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