The oxidative metabolism of arachidonic acid by purified cytochromes P-450

Capdevila, Jorge H.; Parkhill, Linda; Chacos, N.; Okita, Richard T.; Masters, Bettie Sue Siler; Estabrook, Ronald W.

doi:10.1016/0006-291x(81)91597-7

Cited by 124 publications

(38 citation statements)

References 8 publications

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“…Electronic transport of the endoplasmic reticulum and nuclear membrane systems Both systems of intracellular membranes contain cytochromes P450 and b5, which can oxidize unsaturated fatty acids (Capdevila et al, 1981;Ghouleh et al, 2011) and xenobiotics (Chignell, 1979). The cytochromes P450 and b5 are the most powerful oxidizers in vivo, although they can also act as reducing agents.…”

Section: 23mentioning

confidence: 99%

Oxidative Stress and Neurodegenerative Disease

Rivas‐Arancibia¹,

Gallegos-Ríos²,

Gómez-Crisóstomo³

et al. 2011

Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring

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Section: 23mentioning

confidence: 99%

Oxidative Stress and Neurodegenerative Disease

Rivas‐Arancibia¹,

Gallegos-Ríos²,

Gómez-Crisóstomo³

et al. 2011

Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring

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“…A high concentration of mitochondrial SOD ensures no significant O 2 .− accumulation beyond its initial site of production and allows for the generation of H 2 O 2 which has second messenger effects in the cytosol [31,[38][39][40]. The endoplasmic reticulum (ER) is another cellular source of ROS where resident cytochrome P-450 and b 5 family members oxidize unsaturated fatty acids and xenobiotics to generate O 2 .− and H 2 O 2 [41][42][43]. In addition, plasma membrane-associated oxidases such as NADPH oxidases generate ROS by oxidizing intracellular NADPH to reduce O 2 into O 2 .− in order to achieve localized microbicidal function in phagosomes [44][45][46][47].…”

Section: Types and Sources Of Cellular Rosmentioning

confidence: 99%

Reactive oxygen species and cellular oxygen sensing

Cash

Pan

Simon

2007

Free Radical Biology and Medicine

160

100

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Many organisms activate adaptive transcriptional programs to help them cope with decreased oxygen levels, or hypoxia, in their environment. These responses are triggered by various oxygen sensing systems in bacteria, yeast and metazoans. In metazoans, the hypoxia inducible factors (HIFs) mediate the adaptive transcriptional response to hypoxia by upregulating genes involved in maintaining bioenergetic homeostasis. The HIFs in turn are regulated by HIF-specific prolyl hydroxlase activity, which is sensitive to cellular oxygen levels and other factors such as tricarboxylic acid cycle metabolites and reactive oxygen species (ROS). Establishing a role for ROS in cellular oxygen sensing has been challenging since ROS are intrinsically unstable and difficult to measure. However, recent advances in fluorescence energy transfer resonance (FRET)-based methods for measuring ROS are alleviating some of the previous difficulties associated with dyes and luminescent chemicals. In addition, new genetic models have demonstrated that functional mitochondrial electron transport and associated ROS production during hypoxia are required for HIF stabilization in mammalian cells. Current efforts are directed at how ROS mediate prolyl hydroxylase activity and hypoxic HIF stabilization. Progress in understanding this process has been enhanced by the development of the FRET-based ROS probe, an vivo prolyl hydroxylase reporter and various genetic models harboring mutations in components of the mitochondrial electron transport chain.

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“…If COX-2 does not metabolize 5,6-EET or if the metabolites produced are different from those produced by COX-1, selective inhibition of COX-2 may be less effective at reducing 5,6-EET-induced contraction of rabbit intralobar PA than selective inhibition of COX-1. Incubation of [ 14 C]5,6-EET without addition of either COX-1 or COX-2 isoforms, under conditions identical to those in which the enzymes were included, resulted in nonenzymatic hydrolysis of [ 14 C]5,6-EET to the diol, 5,6-dihydroxy-epoxyeicosatrienoic acid and its ␦-lactone as described previously (Capdevila et al, 1981) (Fig. 8A).…”

Section: Identification and Localization Of Cox Isoforms Inmentioning

confidence: 99%

Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries

Moreland¹,

Procknow²,

Sprague³

et al. 2007

J Pharmacol Exp Ther

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Epoxyeicosatrienoic acids (EETs) have been reported to contract intralobar pulmonary arteries (PA) of the rabbit in a cyclooxygenase (COX)-dependent manner. In the present study, we observed that COX-1 and COX-2 isoforms were expressed in freshly isolated PA of healthy rabbits. We examined the hypothesis that both COX isoforms participate in 5,6-EET-induced contraction of rabbit intralobar PA. Selective inhibition of COX-1 with 300 nM 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) prevented 5,6-EET (1 ϫ 10 Ϫ8 -1 ϫ 10 Ϫ5 M)-induced contractions of isolated intralobar rabbit PA rings in a manner similar to that observed with the nonselective cyclooxygenase inhibitor indomethacin at 10 M. Selective inhibition of COX-2 with either 100 nM 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonyl) thiophene (DUP-697) or 3 M N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) shifted the EC 50 value of 5,6-EET-induced PA contraction to the right but with considerably lower efficacy than SC-560. In rabbit PA, 5,6-EET-induced contraction was primarily dependent on COX-1 activity. Differential metabolism of 5,6-EET by COX-1 and COX-2 does not explain the primary dependence of PA contraction on COX-1 activity because 5,6-EET was metabolized similarly by both COX isoforms. COX-1 and -2 were expressed primarily in PA endothelium where COX-1 expression was dense and uniform, whereas COX-2 expression was sparse and nonuniform. 5,6-EET-induced PA contraction was endothelium-dependent. These results suggest that 5,6-EET-induced contraction is primarily dependent on COX-1 activity.

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The oxidative metabolism of arachidonic acid by purified cytochromes P-450

Cited by 124 publications

References 8 publications

Oxidative Stress and Neurodegenerative Disease

Oxidative Stress and Neurodegenerative Disease

Reactive oxygen species and cellular oxygen sensing

Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries

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