Lipoxygenase-mediated transformation of human low density lipoprotein to an oxidized and cytotoxic complex.
We have been studying the mechanisms involved in the oxidative modification of low density lipoprotein (LDL) that lead to its transformation to a cytotoxic complex. Here we examine the direct effect-of soybean lipoxygenase (SLO), a 15-lipoxygenase, on normal human LDL. SLO oxidized LDL and rendered it cytotoxic; agents known to interfere with lipoxygenase activity inhibited this reaction. Enhancement of both the SLO-mediated LDL oxidation and the conversion of LDL to a cytotoxin was observed when either superoxide dismutase or copper (II) (3,5,-diisopropylsalicylic acid)2, both of which dismute superoxide anion, were included during the incubation of SLO with LDL. In contrast, catalase inhibited this reaction in the presence or absence of agents that dismute superoxide anion. Thus, purified lipoxygenase can mediate LDL modification and superoxide anion inhibits this reaction, Furthermore, H2O2 is essential for SLO-mediated LDL oxidation and conversion of LDL to a cytotoxin.
Cathcart
M K
MK
Department of Immunology, Cleveland Clinic Foundation, OH 44195.
McNally
A K
AK
Chisolm
G M
GM
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D002460:Cell Line; D003300:Copper / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000633:toxicity; D008084:Lipoxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D008077:Lipoproteins, LDL; D015117:5,8,11,14-Eicosatetraynoic Acid; D003300:Copper; D008084:Lipoxygenase; D013482:Superoxide Dismutase; D010741:Phospholipases A