Abstract
Group IIA secretory phospholipase A2 is an acute phase enzyme, co-expressed with serum amyloid A protein. Both are present in atherosclerotic lesions. We report that human normal and acute phase high density lipoproteins and low density lipoprotein are effective substrates for human group IIA phospholipase A2. The enzyme hydrolyzed choline and ethanolamine glycerophospholipids at the sn-2 position resulting in an accumulation of the corresponding lysophospholipids, including the unhydrolyzed alkyl and alkenyl ether derivatives. The hydrolysis of acute phase high density lipoprotein was 2- to 3-fold more rapid and intensive than of normal high density lipoprotein. The hydrolysis of lipoproteins was noted at enzyme concentration as low as 0.05 μg/mg protein, which was within the range observed in the circulation in acute and chronic inflammatory diseases. The enzyme hydrolyzed the different molecular species of the residual glycerophospholipids in proportion to their mass, showing no preference for the release of arachidonic acid. Group IIA phospholipase A2 preferentially attacked the hydroxy and hydroperoxy linoleates and possibly other oxygenated fatty acids, which were released from the glycerophospholipids at early times of incubation. There was no effect on the content or molecular species composition of the sphingomyelins or neutral lipids of the lipoproteins. In conclusion, human plasma lipoproteins are the first reported natural biological substrates for human group IIA phospholipase A2. The enhanced hydrolysis of acute phase high density lipoproteins is probably due to its association with serum amyloid A protein, which enhances the activity of the enzyme and may promote its penetration to the lipid monolayer. As sPLA2-induced hydrolysis of the lipoproteins leads to accumulation of lysophosphatidylcholine and potentially toxic oxygenated fatty acids, overexpression of this enzyme may be proatherogenic. —Pruzanski, W., E. Stefanski, F. C. de Beer, M. C. de Beer, P. Vadas, A. Ravandi, and A. Kuksis. Lipoproteins are substrates for human secretory group IIA phospholipase A2: preferential hydrolysis of acute phase HDL. J. Lipid. Res. 39: 2150–2160.
Highlights
Group IIA secretory phospholipase A2 is an acute phase enzyme, co-expressed with serum amyloid A protein
30% of the Low density lipoprotein (LDL) and normal HDL (NHDL) PC was hydrolyzed in 4 h, whereas up to 80% of acute phase HDL (APHDL) PC was hydrolyzed in the same time period
Both NHDL and APHDL were nearly completely hydrolyzed in 8 h, while the LDL was only about 50% hydrolyzed at the same time
Summary
Group IIA secretory phospholipase A2 is an acute phase enzyme, co-expressed with serum amyloid A protein. The enhanced hydrolysis of acute phase high density lipoproteins is probably due to its association with serum amyloid A protein, which enhances the activity of the enzyme and may promote its penetration to the lipid monolayer. Lipoproteins are substrates for human secretory group IIA phospholipase A2: preferential hydrolysis of acute phase HDL. Human secretory non-pancreatic group IIA phospholipase A2 (sPLA2) is expressed as an acute phase protein and its concentration can increase hundreds-fold in the circulation and inflammatory fluids [1]. This could hold implications for LDL metabolism both with respect to clearance by scavenger receptors as well as enhancement of the susceptibility of LDL to lipid peroxidation [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
