CYP2J subfamily P450s in the lung

Expression, localization, and potential functional significance

Darryl C. Zeldin, Julie Foley, Jixiang Ma, James E. Boyle, Jorge M S Pascual, Cindy R. Moomaw, Kenneth B. Tomer, Charles Jr Steenbergen, Shu Wu

Research output: Contribution to journalArticle

Abstract

Cytochrome P450 (P450) monooxygenases catalyze the epoxidation of arachidonic acid to form epoxyeicosatrienoic acids, which modulate bronchial smooth muscle tone and airway transepithelial ion transport. We recently described a new human P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3). Northern analysis of lung RNA using CYP2J cDNA probes demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed in the lung. Immunoblotting of microsomal fractions prepared from human and rat lungs using a polyclonal antibody raised against recombinant human CYP2J2 revealed a single 56-kDa band confirming abundant pulmonary CYP2J2 and CYP2J3 protein expression. Immunohistochemical analysis of formalin-fixed paraffin- embedded human and rat lung sections using the anti-human CYP2J2 IgG and avidin/biotin/peroxidase detection showed that CYP2J proteins were primarily expressed in ciliated epithelial cells lining the airway. Prominent staining was also noted in nonciliated airway epithelial cells, bronchial and pulmonary vascular smooth muscle cells, pulmonary vascular endothelium, and alveolar macrophages, whereas less intense staining was noted in alveolar epithelial cells. Endogenous epoxyeicosatrienoic acids were detected in both human and rat lung using gas chromatography/mass spectrometry, thus providing direct evidence for the in vivo human and rat pulmonary P450 metabolism of arachidonic acid. Based on these data, we conclude that CYP2J2 and CYP2J3 are abundant pulmonary arachidonic acid epoxygenases and that CYP2J products, the epoxyeicosatrienoic acids, are endogenous constituents of human and rat lung. In addition to known effects on airway smooth muscle tone and transepithelial electrolyte transport, the localization of CYP2J proteins to vascular smooth muscle and endothelium suggests that epoxyeicosatrienoic acids may also be involved in the modulation of pulmonary vascular tone.

Original languageEnglish (US)
Pages (from-to)1111-1117
Number of pages7
JournalMolecular Pharmacology
Volume50
Issue number5
StatePublished - Nov 1996
Externally publishedYes

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Lung
Arachidonic Acid
Acids
Vascular Smooth Muscle
Smooth Muscle
Epithelial Cells
Staining and Labeling
Alveolar Epithelial Cells
Proteins
Avidin
Ion Transport
Vascular Endothelium
Alveolar Macrophages
Biotin
Mixed Function Oxygenases
arachidonate epoxygenase
Immunoblotting
Paraffin
Gas Chromatography-Mass Spectrometry
Cytochrome P-450 Enzyme System

ASJC Scopus subject areas

  • Pharmacology

Cite this

Zeldin, D. C., Foley, J., Ma, J., Boyle, J. E., Pascual, J. M. S., Moomaw, C. R., ... Wu, S. (1996). CYP2J subfamily P450s in the lung: Expression, localization, and potential functional significance. Molecular Pharmacology, 50(5), 1111-1117.

CYP2J subfamily P450s in the lung : Expression, localization, and potential functional significance. / Zeldin, Darryl C.; Foley, Julie; Ma, Jixiang; Boyle, James E.; Pascual, Jorge M S; Moomaw, Cindy R.; Tomer, Kenneth B.; Steenbergen, Charles Jr; Wu, Shu.

In: Molecular Pharmacology, Vol. 50, No. 5, 11.1996, p. 1111-1117.

Research output: Contribution to journalArticle

Zeldin, DC, Foley, J, Ma, J, Boyle, JE, Pascual, JMS, Moomaw, CR, Tomer, KB, Steenbergen, CJ & Wu, S 1996, 'CYP2J subfamily P450s in the lung: Expression, localization, and potential functional significance', Molecular Pharmacology, vol. 50, no. 5, pp. 1111-1117.
Zeldin DC, Foley J, Ma J, Boyle JE, Pascual JMS, Moomaw CR et al. CYP2J subfamily P450s in the lung: Expression, localization, and potential functional significance. Molecular Pharmacology. 1996 Nov;50(5):1111-1117.
Zeldin, Darryl C. ; Foley, Julie ; Ma, Jixiang ; Boyle, James E. ; Pascual, Jorge M S ; Moomaw, Cindy R. ; Tomer, Kenneth B. ; Steenbergen, Charles Jr ; Wu, Shu. / CYP2J subfamily P450s in the lung : Expression, localization, and potential functional significance. In: Molecular Pharmacology. 1996 ; Vol. 50, No. 5. pp. 1111-1117.
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abstract = "Cytochrome P450 (P450) monooxygenases catalyze the epoxidation of arachidonic acid to form epoxyeicosatrienoic acids, which modulate bronchial smooth muscle tone and airway transepithelial ion transport. We recently described a new human P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3). Northern analysis of lung RNA using CYP2J cDNA probes demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed in the lung. Immunoblotting of microsomal fractions prepared from human and rat lungs using a polyclonal antibody raised against recombinant human CYP2J2 revealed a single 56-kDa band confirming abundant pulmonary CYP2J2 and CYP2J3 protein expression. Immunohistochemical analysis of formalin-fixed paraffin- embedded human and rat lung sections using the anti-human CYP2J2 IgG and avidin/biotin/peroxidase detection showed that CYP2J proteins were primarily expressed in ciliated epithelial cells lining the airway. Prominent staining was also noted in nonciliated airway epithelial cells, bronchial and pulmonary vascular smooth muscle cells, pulmonary vascular endothelium, and alveolar macrophages, whereas less intense staining was noted in alveolar epithelial cells. Endogenous epoxyeicosatrienoic acids were detected in both human and rat lung using gas chromatography/mass spectrometry, thus providing direct evidence for the in vivo human and rat pulmonary P450 metabolism of arachidonic acid. Based on these data, we conclude that CYP2J2 and CYP2J3 are abundant pulmonary arachidonic acid epoxygenases and that CYP2J products, the epoxyeicosatrienoic acids, are endogenous constituents of human and rat lung. In addition to known effects on airway smooth muscle tone and transepithelial electrolyte transport, the localization of CYP2J proteins to vascular smooth muscle and endothelium suggests that epoxyeicosatrienoic acids may also be involved in the modulation of pulmonary vascular tone.",
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N2 - Cytochrome P450 (P450) monooxygenases catalyze the epoxidation of arachidonic acid to form epoxyeicosatrienoic acids, which modulate bronchial smooth muscle tone and airway transepithelial ion transport. We recently described a new human P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3). Northern analysis of lung RNA using CYP2J cDNA probes demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed in the lung. Immunoblotting of microsomal fractions prepared from human and rat lungs using a polyclonal antibody raised against recombinant human CYP2J2 revealed a single 56-kDa band confirming abundant pulmonary CYP2J2 and CYP2J3 protein expression. Immunohistochemical analysis of formalin-fixed paraffin- embedded human and rat lung sections using the anti-human CYP2J2 IgG and avidin/biotin/peroxidase detection showed that CYP2J proteins were primarily expressed in ciliated epithelial cells lining the airway. Prominent staining was also noted in nonciliated airway epithelial cells, bronchial and pulmonary vascular smooth muscle cells, pulmonary vascular endothelium, and alveolar macrophages, whereas less intense staining was noted in alveolar epithelial cells. Endogenous epoxyeicosatrienoic acids were detected in both human and rat lung using gas chromatography/mass spectrometry, thus providing direct evidence for the in vivo human and rat pulmonary P450 metabolism of arachidonic acid. Based on these data, we conclude that CYP2J2 and CYP2J3 are abundant pulmonary arachidonic acid epoxygenases and that CYP2J products, the epoxyeicosatrienoic acids, are endogenous constituents of human and rat lung. In addition to known effects on airway smooth muscle tone and transepithelial electrolyte transport, the localization of CYP2J proteins to vascular smooth muscle and endothelium suggests that epoxyeicosatrienoic acids may also be involved in the modulation of pulmonary vascular tone.

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