Conversion of arachidonic acid to two novel products by a cytochrome P450-dependent mixed-function oxidase in polymorphonuclear leukocytes

Bednar, Martin M.; Schwartzman, Michal Laniado; Ibraham, N G; McGiff, John C.; Mullane, Kevin

doi:10.1016/0006-291x(84)90269-9

Cited by 21 publications

(9 citation statements)

References 11 publications

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“…12 The localization of AHH activity found in the present study lends support to such a proposal, since endotheliumdependent responses have also been observed in the pig aorta. 19 Moreover, cells of the medulla of the kidney 20 as well as polymorphonuclear leukocytes 21 contain cytochrome P-450-dependent enzymes capable of generating vasodilator products from arachidonic acid.…”

Section: Discussionmentioning

confidence: 99%

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Abraham¹,

Pinto²,

Mullane³

et al. 1985

Hypertension

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SUMMARY Cytochrome P-450-dependent mixed function oxidase activity is present in vascular tissue; however, as far as we could determine, the distribution of monooxygenase activity across the blood vessel wall has not previously been assessed. The aryl-hydrocarbon hydroxylase activity was examined by metabolism of benzo[a]pyrene in microsomes prepared from intimal and smooth muscle cell scrapings of the hog thoracic aorta. Microsomes of intimal cells comprising 95 % endothelial cells showed an approximately 2.5-fold increase in aryl-hydrocarbon hydroxylase activity compared with that in microsomes prepared from medial smooth muscle cells. Michaelis-Mentin kinetics for the intimal enzyme yielded an apparent K m value of 11.11 /xM and an apparent V max of 3-0H benzo[a]pyrene of 40 pmol/mg protein/10 min. Aryl-hydrocarbon hydroxylase activity was dependent on nicotinamide adenine dinucleotide phosphate and was inhibited by 7,8 benzoflavone, SKF 525A, and carbon monoxide. The localization of cytochrome P-450-dependent mixed function oxidase primarily to the intimal surface of the aorta may indicate a role for this enzyme system in vasoregulation and the pathogenesis of atherosclerosis. (Hypertension 7: 899-904, 1985)

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Section: Discussionmentioning

confidence: 99%

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Abraham¹,

Pinto²,

Mullane³

et al. 1985

Hypertension

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“…However, a similar action on endothelial cells could not account for the inhibition observed in calcium-free solution. Proadifen does not appear to inhibit 5-lipoxygenase, since lipoxygenase product formation was enhanced in polymorphonuclear leucocytes (Bednar et al 1984). Therefore, it seems likely that cytochrome P-450 metabolites may be more important mediators of endothelium-dependent dilatation than lipoxygenase products of arachidonate.…”

Section: Discussionmentioning

confidence: 97%

Endothelium‐dependent Vasodilatation in Bovine Coronary Arteries: Calcium Dependence and Inhibition by Proadifen

Macdonald

Dubbin

Dusting

1986

Clin Exp Pharma Physio

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Vasodilator responses were examined in bovine coronary artery rings preconstricted with the thromboxane-mimetic, U46619. A23187 produced endothelium-dependent vasodilatation that was abolished in calcium-free solution. In contrast, endothelium-dependent vasodilatation produced by arachidonic acid was not altered in calcium-free solution. In calcium-free solution, indomethacin (10 mumol/l) did not affect arachidonate-induced relaxations whereas BW755C (100 mumol/l) reduced relaxations to low concentrations of arachidonate, and proadifen (SKF-525A, 1 mmol/l) abolished them at all concentrations. Endothelium-independent relaxations produced by glyceryl trinitrate were not affected by proadifen (1 mmol/l). It is clear that arachidonic acid bypasses a calcium-dependent step in the release of endothelium-derived relaxing factor, perhaps acting as an intermediate precursor. The data support the hypothesis that a cytochrome P-450 mono-oxygenase may also be involved.

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“…Metabolism of AA via cytochrome P-450 has been observed in several tissues including bone marrow cells, macrophages, endothelial cells, and neutrophils (85)(86)(87). Several studies have demonstrated that some of the cytochrome P-450-AA metabolites possess a wide range of biologic activities.…”

Section: Role Of Cytochrome P-450 In Hematopoiesismentioning

confidence: 99%

“…Studies over the past few years have revealed that this novel cytochrome P-450-dependent monooxygenase system for the metabolism of AA does exist in hemopoietic cells (85)(86)(87). The three pathways for AA metabolism are represented in Figure 4.…”

Section: Role Of Cytochrome P-450 In Hematopoiesismentioning

confidence: 99%

“…Their metabolites, prostaglandins, hydroxyeicosatetraenoic acid (HETE), and leukotrienes, have been implicated in the modulation of cell proliferation and differentiation and have both enhancing and inhibitory effects on the hemopoietic system (81)(82)(83)(84). However, it is becoming evident that compounds of a newly discovered branch of the AA cascade, the cytochrome P-450dependent pathway or third pathway, are very important to the hemopoietic system (70,(85)(86)(87).…”

Section: Role Of Cytochrome P-450 In Hematopoiesismentioning

confidence: 99%

See 1 more Smart Citation

Physiologic Role of Heme and Cytochrome P-450 in Hematopoietic Cells

Lutton

Levere²,

Abraham³

1991

Experimental Biology and Medicine

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Conversion of arachidonic acid to two novel products by a cytochrome P450-dependent mixed-function oxidase in polymorphonuclear leukocytes

Cited by 21 publications

References 11 publications

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Endothelium‐dependent Vasodilatation in Bovine Coronary Arteries: Calcium Dependence and Inhibition by Proadifen

Physiologic Role of Heme and Cytochrome P-450 in Hematopoietic Cells

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