Enhanced hydrolysis of phosphatidylcholine by human group II non-pancreatic secreted phospholipase A2 as a result of interfacial activation by specific anions. Potential role of cholesterol sulphate.
The extracellular concentration of the Group II human non-pancreatic secreted phospholipase A2 (hnpsPLA2) is elevated in a variety of inflammatory disorders. This enzyme is remarkable because it demonstrates almost zero activity with egg phosphatidylcholine (PC) or synthetic dioleoyl-phosphatidylcholine (DOPC) as substrate, but expresses high activity with the anionic phospholipid dioleoyl-phosphatidylglycerol (DOPG), a feature shared with the Group II enzyme from rat liver. The presence of certain membrane-bound anions can enhance hydrolysis of PC by the mammalian secreted PLA2S. In this study the ability of various non-polar anions to stimulate DOPC hydrolysis by secreted PLA2S has been investigated. The naturally occurring membrane anion, cholesterol sulphate, was particularly effective in stimulating the hydrolysis of both DOPC and also 1-stearoyl-2-arachidonyl phosphatidylcholine by hnpsPLA2. Activation of DOPC hydrolysis was also achieved with dioleoyl-phosphatidylserine (DOPS); however, DOPS was less effective than cholesterol sulphate. In contrast, the dianion dioleoyl-phosphatidic acid, a known activator of pig pancreatic PLA2, failed to activate the human enzyme. It remains to be established whether cell plasma-membrane hydrolysis by extracellular hnpsPLA2 can be activated in vivo by the presence of suitable membrane anions such as cholesterol sulphate and thus promote an inflammatory response within the cell.
Kinkaid
A R
AR
Department of Biochemistry, University of Southampton, UK.
Wilton
D C
DC
D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions; D001647:Bile Acids and Salts / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology; D010712:Phosphatidic Acids / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D013552:Swine
D000838:Anions; D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; C042511:1,2-dioleoylphosphatidylserine; D010741:Phospholipases A; D054467:Phospholipases A2; C017251:1,2-oleoylphosphatidylcholine; C007045:cholesteryl sulfate