Effect of homocysteine on arachidonic acid release in human platelets.
BACKGROUND
It has been suggested that homocysteine is implicated in the risk of atherosclerosis and thrombosis. The pathogenic mechanism has not been clarified, but oxygen-free species produced by the homocysteine metabolism and auto-oxidation could have a role.


METHODS
We have studied the effect of homocysteine on arachidonic acid release in human platelets. Two important products of arachidonic acid metabolism - thromboxane B2 (TXB2) and reactive oxygen species (ROS) - have been assayed.


RESULTS
Results indicate that homocysteine induces arachidonic acid release that is partially inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA). Platelet incubation with homocysteine significantly increases basal levels of TXB2 and ROS. The effect is time- and dose-dependent. The TXB2 formation is strictly correlated with the arachidonic acid release. Moreover, ROS accumulation is largely inhibited by ETYA and partially reduced by diphenyleneiodonium (DPI), suggesting the involvement both of enzymes metabolising arachidonic acid (cyclooxygenase, lipooxygenase, cytochrome P450 monooxygenase) and of NAD(P)H oxidase.


CONCLUSIONS
Homocysteine induces oxidative stress in human platelets in vitro. The unbalance in platelet redox-state and the increased TXB2 formation may generate hyperactivation, contributing to a thrombogenic state leading to cardiovascular diseases.
Signorello
M G
MG
Department of Experimental Medicine, Biochemistry Section, University of Genova, Genova, Italy.
Pascale
R
R
Leoncini
G
G
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis; D013929:Thromboxane B2 / Q000032:analysis
D009097:Multienzyme Complexes; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D006710:Homocysteine; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D013929:Thromboxane B2; C007517:diphenyleneiodonium; D003577:Cytochrome P-450 Enzyme System; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases