Key result
Hepatic lipase-mimicking peptide displaces HL from cell surfaces and changes structure with heparin.
A novel mimetic peptide of the human hepatic lipase heparin binding domain successfully displaces HL from the cell surface, providing a potential mechanism to enhance reverse cholesterol transport.
May aid mechanistic studies of hepatic lipase; leaves open clinical relevance for reverse cholesterol transport.
Human hepatic lipase (HL) hydrolyzes triglycerides and phospholipids within circulating lipoproteins. HL is bound to heparan sulfate proteoglycans (HPSG) and is believed to function as a head to tail homodimer. The hydrolysis of lipids within high-density lipoproteins (HDL) liberates preβ1-HDL that can accept extrahepatic cholesterol during the anti-atherogenic process of reverse cholesterol transport. Displacing HL from HSPG to the bloodstream allows HL to access more HDL, ultimately generating more preβ1-HDL. We hypothesized that a peptide mimicking the major heparin binding domain (HBD) of HL would displace HL from HSPG. To test this hypothesis, we used a fusion protein with a cleavable peptide containing the major HBD of HL. The fusion protein retained the heparin binding properties of human HL, which suggests that the HL-HSPG association may not require a homodimer structure. Using HEK293 cells expressing HL, we showed that the fusion protein displaces HL from the cell surface at 4°C. We also sought to determine structural properties of the cleaved peptide. Circular dichroism studies showed the mimetic peptide had a propensity to become α-helical in the presence of trifluoroethanol. Proton nuclear magnetic resonance experiments further show that the peptide undergoes a structural change in the presence of heparin. Overall, we have generated a functional peptide that mimics the HBD properties of HL and it can displace cell surface HL. We anticipate testing whether it can ultimately increase the generation of preβ1-HDL and improve cholesterol efflux. Funded by the Canadian Institutes of Health Research (#RNL-125110), and the Research & Development Corporation of Newfoundland and Labrador (#5404.1358.102).
No takes yet. Share an insight, caveat, or question.
Coady et al. (2015) studied this question. Mimetic peptide of human hepatic lipase (HL) major heparin binding domain was evaluated on Displacement of HL from cell surface and structural properties. A peptide mimicking the major heparin binding domain of human hepatic lipase successfully displaced HL from the surface of HEK293 cells and underwent structural changes in the presence of heparin.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: