Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol

Baiba K. Gillard, Corina Rosales, Biju K. Pillai, Hu Yu Lin, Harry S. Courtney, Henry J. Pownall

Research output: Contribution to journalArticle

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Abstract

Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ∼400000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins, and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E-dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. The uptake of [ 3H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[3H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[3H]CE uptake by both receptors. RAP and heparin inhibit CERM-[3H]CE but not HDL-[3H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful.

Original languageEnglish (US)
Pages (from-to)9866-9873
Number of pages8
JournalBiochemistry
Volume49
Issue number45
DOIs
StatePublished - Nov 16 2010

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Plasma (human)
Cholesterol Esters
HDL Cholesterol
Hepatocytes
HDL Lipoproteins
Microemulsions
Low Density Lipoprotein Receptor-Related Protein-1
CD36 Antigens
Plasmas
opacity factor
LDL Receptors
Apolipoproteins E
Cricetulus
Ovary
Liver
Lipoprotein Receptors
Streptococcus pyogenes
Apolipoprotein A-I
Hep G2 Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Gillard, B. K., Rosales, C., Pillai, B. K., Lin, H. Y., Courtney, H. S., & Pownall, H. J. (2010). Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol. Biochemistry, 49(45), 9866-9873. https://doi.org/10.1021/bi101412m

Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol. / Gillard, Baiba K.; Rosales, Corina; Pillai, Biju K.; Lin, Hu Yu; Courtney, Harry S.; Pownall, Henry J.

In: Biochemistry, Vol. 49, No. 45, 16.11.2010, p. 9866-9873.

Research output: Contribution to journalArticle

Gillard, BK, Rosales, C, Pillai, BK, Lin, HY, Courtney, HS & Pownall, HJ 2010, 'Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol', Biochemistry, vol. 49, no. 45, pp. 9866-9873. https://doi.org/10.1021/bi101412m
Gillard, Baiba K. ; Rosales, Corina ; Pillai, Biju K. ; Lin, Hu Yu ; Courtney, Harry S. ; Pownall, Henry J. / Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol. In: Biochemistry. 2010 ; Vol. 49, No. 45. pp. 9866-9873.
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