Apolipoprotein C-III-1 activates lysosomal sphingomyelinase in vitro.
Apolipoprotein (apo)C-III-1 from human very low density lipoprotein stimulates 14-fold the activity of lysosomal sphingomyelinase from human fibroblasts. At the sphingomyelin concentrations tested, maximal stimulation was obtained with 5 microM apoC-III-1 or apoC mixture. Apolipoproteins A-I, A-II, B, and C-I conferred little or no stimulation. Sphingomyelinase was stimulated 20-fold by lysophosphatidylcholine with an optimum concentration of 70 microM using 0.3 mM substrate. Sphingomyelinase activity was inhibited by concentrations of apoC-III-1 and lysophosphatidylcholine three- to fivefold above stimulatory levels. Triton X-100 activated sphingomyelinase 300-fold with a pH optimum of 5.0, while the pH optimum with the biological activators was 4.0. These results raise the possibility of an in vivo activity for the biological activators. The proteins that enter lysosomes as part of a lipoprotein complex may activate lysosomal enzymes that degrade the lipid components.
D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000494:pharmacology*; D001056:Apolipoproteins C; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology; D012867:Skin; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism
D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001056:Apolipoproteins C; D008244:Lysophosphatidylcholines; D013109:Sphingomyelins; D011092:Polyethylene Glycols; D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase