Apolipoprotein C-1 inhibits the hydrolysis by phospholipase A2 of phospholipids in liposomes and cell membranes.

A small polypeptide isolated from human serum inhibits the action of phospholipase A2 on dipalmitoylglycerol phosphocholine vesicles. Sequence analysis revealed the protein to be apolipoprotein C-1, a major component of very light-density lipoprotein. The inhibiting efficiency is increased by one order of magnitude after 10 min preincubation of the protein with the substrate, but not the enzyme. It also depends on the concentration of the phospholipid. IC50 is about 0.5 microM at 0.2 mM DPPC and 1 microM at 1 mM DPPC. Apolipoprotein C-1 is also inhibitory in a more physiological system: in broken human leukemia cells (HL-60 cells) it inhibits the release by endogenous phospholipases of arachidonic acid from membrane phospholipids. The effective concentrations correspond to those found in the serum. It is concluded that apolipoprotein C-1 and similar phospholipid-binding proteins may act as phospholipase inhibitors by blocking the access to the substrate.