title: Mouse aortic muscle cells respond to oxygen following cytochrome P450 3A13 gene transfer.
abstract: We have previously shown that a cytochrome P450 (CYP450) hemoprotein from the 3A subfamily CYP3A13 for the mouse, serves as the sensor in the contraction of the ductus arteriosus in response to increased oxygen tension. In addition, we have identified endothelin-1 (ET-1) as the effector for this response. Here, we examined whether Cyp3a13 gene transfer confers oxygen sensitivity to cultured muscle cells from mouse aorta. Coincidentally, we determined whether the same hemoprotein is normally present in the vessel. Cyp3a13-transfected aortic cells responded to oxygen, whereas no significant response was seen in native cells or in cells transfected with an empty vector. Furthermore, this oxygen effect was curtailed by the ET-1/ETA receptor antagonist BQ-123. We also found that CYP3A13 occurs naturally in aortic tissue and its isolated muscle cells in culture. We conclude that CYP3A13 is involved in oxygen sensing, and its action in the transfected muscle cells of the aorta, as in the native cells of the ductus, takes place through a linkage to ET-1. However, the response of aortic muscle to oxygen, conceivably entailing the presence of CYP3A13 at some special site, is not seen in the native situation, and may instead unfold upon transfection of the parent gene.
authors: Institute of Life Sciences, Scuola Superiore Sant'Anna, 56100 Pisa, Italy.
authors: Enrica
authors: E
authors: Ciofini
authors: Francesca
authors: F
authors: Scebba
authors: Stefano
authors: S
authors: Luin
authors: Daria
authors: D
authors: Sodini
authors: Debora
authors: D
authors: Angeloni
authors: Flavio
authors: F
authors: Coceani
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D019332:Endothelin-1; D006420:Hemeproteins; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C496509:Cyp3a13 protein, mouse; D051544:Cytochrome P-450 CYP3A; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D010100:Oxygen; D002118:Calcium