Effects of peroxynitrite on plasma components of the reverse cholesterol transport pathway.
Elimination of cholesterol from arterial tissue, crucial in limiting atherogenesis, may be achieved via high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT); components of this pathway can be modulated by oxidative stress. Here we have examined the relations between cholesterol efflux, esterification and transfer in human plasma treated with the powerfully reactive nitrogen species, peroxynitrite. Cellular cholesterol efflux to whole plasma, or to peroxynitrite-modified HDL3, was relatively insensitive to peroxynitrite, as was the transfer of esterified cholesterol. However, plasma cholesterol esterification, via lecithin:cholesterol acyltransferase (LCAT), was markedly inhibited, both directly and indirectly, by peroxynitrite treatment, implying inefficient RCT follows HDL sequestration of cellular cholesterol.
Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, London, UK. agraham@rfhsm.ac.uk
A
A
Graham
D V
DV
Vinogradov
J S
JS
Owen
D001692:Biological Transport; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood
D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D009566:Nitrates; C039642:peroxynitric acid; D007862:Phosphatidylcholine-Sterol O-Acyltransferase