The genes of all seven CYP3A isoenzymes identified in the equine genome are expressed in the airways of horses.
Abstract: In the present study, we examined the gene expression of cytochrome P450 3A (CYP3A) isoenzymes in the tracheal and bronchial mucosa and in the lung of equines using TaqMan probes. The results show that all seven CYP3A isoforms identified in the equine genome, that is, CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97 and CYP3A129, are expressed in the airways of the investigated horses. Though in previous studies, CYP3A129 was found to be absent in equine intestinal mucosa and liver, this CYP3A isoform is expressed in the airways of horses. The gene expression of the CYP3A isoenzymes varied considerably between the individual horses studied. However, in most of the horses CYP3A89, CYP3A93, CYP3A96, CYP3A97 and CYP3A129 were expressed to a high extent, while CYP3A94 and CYP3A95 were expressed to a low extent in the different parts of the airways. The CYP3A isoenzymes present in the airways may play a role in the metabolic degradation of inhaled xenobiotics. In some instances, the metabolism may, however, result in bioactivation of the xenobiotics and subsequent tissue injury.
© 2012 John Wiley & Sons Ltd.
Publication Date: 2012-09-12 PubMed ID: 22966936DOI: 10.1111/jvp.12012Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research observes the expression of all seven CYP3A isoenzymes recognised in the horse’s genome within their airway systems. Despite past studies showing the absence of the CYP3A129 isoform in the intestinal mucosa and liver, it is expressed in the horses’ airways, which could play a role in breaking down inhaled foreign substances.
Investigating Gene Expression of CYP3A Isoenzymes
- The researchers studied the gene expression of cytochrome P450 3A (CYP3A) isoenzymes in the tracheal and bronchial mucosa and in the lung of horses. These crazy isoenzymes are enzymes produced by the CYP3A subfamily of genes that have a role in the metabolism of xenobiotics (substances foreign to a living organism).
- The study used TaqMan probes, a commonly used technique for gene expression analysis, to examine the expression of these enzymes.
- Specifically, they looked at seven isoforms identified in the equine genome: CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97, and CYP3A129.
Findings of Gene Expression in Horses’ Airways
- All these CYP3A isoforms were found to be expressed in the airways of the studied horses, a new finding as CYP3A129 was previously thought to be absent in the equine intestinal mucosa and liver.
- However, the level of gene expression for these CYP3A isoenzymes varied considerably between the horses studied. CYP3A89, CYP3A93, CYP3A96, CYP3A97, and CYP3A129 were highly expressed in most horses, while CYP3A94 and CYP3A95 were expressed to a lesser extent.
Potential Functional Roles of CYP3A Isoenzymes
- The researchers suggest that the CYP3A isoenzymes identified in the airways might play a crucial role in the metabolic degradation of inhaled xenobiotics. This indicates horses’ potential capacity to break down foreign substances they inhale, which could have implications for their health.
- However, they also note that in some cases, the metabolism of these foreign substances may lead to their activation rather than their degradation, which could potentially cause tissue injury. This caveat suggests more research is needed to understand the impact and applications of these findings.
Cite This Article
APA
Tydén E, Löfgren M, Hakhverdyan M, Tjälve H, Larsson P.
(2012).
The genes of all seven CYP3A isoenzymes identified in the equine genome are expressed in the airways of horses.
J Vet Pharmacol Ther, 36(4), 370-375.
https://doi.org/10.1111/jvp.12012 Publication
Researcher Affiliations
- Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. eva.tyden@slu.se
MeSH Terms
- Animals
- Cytochrome P-450 CYP3A / classification
- Cytochrome P-450 CYP3A / genetics
- Cytochrome P-450 CYP3A / metabolism
- Female
- Gene Expression Regulation, Enzymologic / physiology
- Genome
- Horses / genetics
- Horses / metabolism
- Isoenzymes
- Male
- Respiratory System / enzymology
- Respiratory System / metabolism
Citations
This article has been cited 5 times.- Kim KH, Park JW, Yang YM, Song KD, Cho BW. Effect of methylsulfonylmethane on oxidative stress and CYP3A93 expression in fetal horse liver cells.. Anim Biosci 2021 Feb;34(2):312-319.
- Löfgren M, Larsson P, Lindberg R, Hörnaeus K, Tydén E. Expression of xenobiotic metabolising enzymes in lungs of horses with or without histological evidence of lower airway inflammation.. Vet Med Sci 2021 Jan;7(1):16-24.
- Jacobson GA, Raidal S, Robson K, Narkowicz CK, Nichols DS, Haydn Walters E. Bronchopulmonary pharmacokinetics of (R)-salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses.. Br J Clin Pharmacol 2017 Jul;83(7):1436-1445.
- Dettwiler R, Schmitz AL, Plattet P, Zielinski J, Mevissen M. Heterologous expression of equine CYP3A94 and investigation of a tunable system to regulate co-expressed NADPH P450 oxidoreductase levels.. PLoS One 2014;9(11):e113540.
- Tydén E, Tjälve H, Larsson P. Gene and protein expression and cellular localisation of cytochrome P450 enzymes of the 1A, 2A, 2C, 2D and 2E subfamilies in equine intestine and liver.. Acta Vet Scand 2014 Oct 8;56(1):69.
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