Interactions between nitric oxide and arachidonic acid in lung epithelial cells: possible roles for peroxynitrite and superoxide.
This study investigated interactions between nitric oxide synthesis and phospholipase A2 (PLA2) activation in lung epithelial cells. Nitrite formation, inducible nitric oxide synthase expression, and [3H]arachidonic acid (AA) release were determined following treatment with: (1) the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl esther (L-NAME) and aminoguanidine; (2) arachidonyl trifluoromethyl ketone (AACOCF3), a specific cytosolic PLA2 inhibitor; (3) S-morpholinosydnonimine (SIN-1), a nitric oxide donor which provokes peroxynitrite formation; (4) trolox, a free radical scavenger, and (5) the AA release agonists calcium ionophore, phorbol 12-myristate 13-acetate, and sodium vanadate. The results demonstrated that (1) L-NAME and aminoguanidine inhibited agonist-induced AA release by 40 and 65%, respectively; (2) AACOCF3 inhibited nitrite formation and inducible nitric oxide synthase expression in a dose-dependent manner; (3) SIN-1, together with AA release agonists, significantly increased the AA output, and (4) trolox counteracted the SIN-1 effects. Our results demonstrate cross talk between nitric oxide synthase and PLA(2) pathways, with a possible intermediary role for peroxynitrite and superoxide.
Offer
Sarit
S
Institute of Biochemistry, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
Eliraz
Abraham
A
Fink
Gershon
G
Stark
Aliza H
AH
Madar
Zecharia
Z
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D054467:Phospholipases A2; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013481:Superoxides; D030421:Peroxynitrous Acid; D016718:Arachidonic Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D010741:Phospholipases A; D054467:Phospholipases A2