Proteomic profiling of cellular responses to Carvedilol enantiomers in vascular smooth muscle cells by iTRAQ-coupled 2-D LC-MS/MS.
Carvedilol is a third-generation beta-blocker, with the S-enantiomer being more active than the R-enantiomer. Clinically, it has been used in the treatment of hypertension, congestive heart failure and angina pectoris. Each enantiomer of Carvedilol exhibits differential pharmacological effects. However, the cellular effects of individual enantiomer are not well understood. To gain insights into how each enantiomer affects cells, we analysed differential protein expression levels in vascular smooth muscle cells (A7r5) incubated separately with S- and R-Carvedilol by iTRAQ-coupled 2-D LC-MS/MS approach. Thirteen proteins were identified with statistically significant changes in cells incubated with S-Carvedilol, while the changes of most proteins incubated with R-Carvedilol were less significant. Among these proteins, actin in aortic smooth muscle (ACTA2), calmodulin, S100-A6, S100-A10, S100-A11, thioredoxin, lactadherin and heat-shock protein 105 kDa were found to be closely relevant with the clinical effects of Carvedilol. Furthermore, the changes in protein levels were validated by Western blot. Our findings thus provided molecular evidence on a comprehensive protein profile on Carvedilol-cell interaction, which may shed new light in molecular events underlying Carvedilol treatment.
Wang
Mingxuan
M
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Wang
Xiujuan
X
Ching
Chi Bun
CB
Chen
Wei Ning
WN
D000199:Actins / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002460:Cell Line; D002853:Chromatography, Liquid; D020869:Gene Expression Profiling; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D040901:Proteomics; D051381:Rats; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D013879:Thioredoxins / Q000378:metabolism
D000199:Actins; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D013879:Thioredoxins