MOUSE AORTIC MUSCLE CELLS RESPOND TO OXYGEN FOLLOWING CYTOCHROME P-450 3A13 GENE TRANSFER

We have previously shown that a cytochrome P450 (CYP450) hemoprotein from the 3A subfamily, CYP3A13 for the mouse, serves as sensor in the contraction of the ductus arteriosus to oxygen. In addition, we have identified in endothelin-1 (ET-1) 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, while no significant response was seen in native cells and 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 committed to 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.