Investigation of chiralities of propranolol and atenolol by comparative proteomic analysis of vascular smooth muscle cells.
Date of Issue2009
School of Chemical and Biomedical Engineering
Propranolol is a nonselective beta-blocker exerting blocking effect on the beta-adrenergic receptors, with the S-enantiomer being more active than the R-enantiomer. Utilization of iTPvAQ coupled with two-dimensional LC-MS/MS system, we report here the first study of protein profiles in vascular smooth muscle cells (A7r5) in response to two individual enantiomers of propranolol, respectively. In this study four categories of cellular proteins including cytoskeletal proteins, signaling molecules, metabolic enzymes and those associated with DNA synthesis/protein translation showed differentially expressed protein levels. The higher protein levels of several enzymes involved in cellular anabolism and antioxidant activity in S-enantiomer of propranolol-incubated A7r5 cells, as revealed by LC MS/ MS, was further validated by real-time PCR. Significantly, the increase in the anabolic activity associated with the higher level of metabolic enzymes was also supported by the higher intracellular concentration of the metabolic cofactor NAD+, which was the product resulting from oxidation of NADH. The higher expression level of thioredoxin might account for increased antioxidant activity, as indicated by the lower ROS level in S-enantiomer of propranolol-incubated cells than that for R-enantiomer of propranolol-incubated cells and control ones.
Nanyang Technological University