12-lipoxygenase in opioid-induced delayed cardioprotection: gene array, mass spectrometric, and pharmacological analyses. Circ Res 2003 Apr 04;92(6):676-82
Date
03/08/2003Pubmed ID
12623876DOI
10.1161/01.RES.0000065167.52922.F6Scopus ID
2-s2.0-0344406762 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
12-lipoxygenase (12-LO) has been shown to be a factor in acute ischemic preconditioning (IPC) in the isolated rat heart; however, no studies have been reported in delayed PC. We characterized the role of 12-LO in an intact rat model of delayed PC induced by a delta-opioid agonist SNC-121 (SNC). Rats were pretreated with SNC and allowed to recover for 24 hours. They were then treated with either baicalein or phenidone, 2 selective 12-LO inhibitors. In addition, SNC-pretreated rats had plasma samples isolated at different times after ischemia-reperfusion for liquid chromatographic-mass spectrometric analysis of the major metabolic product of 12-LO, 12-HETE. Similar studies were conducted with inhibitors. Gene array data showed a significant induction of 12-LO message (P<0.05) after opioid pretreatment. This induction in 12-LO mRNA was confirmed by real-time polymerase chain reaction, and 12-LO protein expression was enhanced by SNC pretreatment at 24 hours relative to vehicle treatment. Both baicalein and phenidone attenuated the protective effects of SNC pretreatment on infarct size (50+/-4% and 42+/-3% versus 29+/-2%, P<0.05, respectively). No significant differences were observed in 12-HETE concentrations between baseline control and SNC-treated rats. However, 12-HETE concentrations were increased significantly at both 15 minutes during ischemia and at 1 hour of reperfusion in the SNC-treated rats compared with controls. Baicalein and phenidone attenuated the increase in 12-HETE at 1 hour of reperfusion. These data suggest that SNC-121 appears to enhance message and subsequently the activity and expression of 12-LO protein during times of stress, resulting in delayed cardioprotection.
Author List
Patel HH, Fryer RM, Gross ER, Bundey RA, Hsu AK, Isbell M, Eusebi LO, Jensen RV, Gullans SR, Insel PA, Nithipatikom K, Gross GJMESH terms used to index this publication - Major topics in bold
12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAnimals
Arachidonate 12-Lipoxygenase
Arachidonic Acid
Benzamides
Blotting, Western
Cardiotonic Agents
Enzyme Inhibitors
Gene Expression Profiling
Hemodynamics
Ischemic Preconditioning, Myocardial
Kinetics
Lipoxygenase Inhibitors
Male
Myocardial Reperfusion Injury
Myocardium
Oligonucleotide Array Sequence Analysis
Piperazines
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta
Reverse Transcriptase Polymerase Chain Reaction
Spectrometry, Mass, Electrospray Ionization
