iTRAQ-Coupled 2D LC-MS/MS Analysis on Protein Profile in Vascular Smooth Muscle Cells Incubated with S- and R-Enantiomers of Propranolol: Possible Role of Metabolic Enzymes Involved in C
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- 作者：Jianjun Sui ; Tuan Lin Tan ; Jianhua Zhang ; Chi Bun Ching ; Wei Ning Chen
- 刊名：Journal of Proteome Research
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：6
- 期：5
- 页码：1643 - 1651
- 全文大小：267K
- 年卷期：v.6,no.5(May 2007)
- ISSN：1535-3907
文摘
Propranolol is a nonselective 
ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-blocker of theges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-adrenergic receptors, and the S-enantiomer is moreactive compared with the R-enantiomer. Clinically, it hasbeen shown to be effective in hypermetabolic burnpatients by decreasing cardiac work, protein catabolism,and lipolysis. While gene expression profiles have recently been reported in children receiving propranololtreatment, variations from one individual to another mayhave influenced the data analysis. Using iTRAQ-coupled2D LC-MS/MS analysis, we report here the first study ofprotein profile in vascular smooth muscle cells incubatedseparately with the two enantiomers of propranolol. Fourtypes of cellular proteins including metabolic enzymes,signaling molecules, cytoskeletal proteins, and thoseinvolved in DNA synthesis/protein translation displayedchanges. The higher protein level of a number of enzymesinvolved in cellular anabolism and antioxidant activity incells incubated with the S-enantiomer, as revealed by LC-MS/MS, was further supported by real-time PCR andWestern blot analyses. Significantly, the increase in theanabolic activity associated with the higher level ofmetabolic enzymes was also supported by the higherintracellular concentration of the metabolic cofactor NAD+which was a result of an increased oxidation of NADH.Our findings therefore provide molecular evidence onmetabolic effect associated with propranolol treatment.The metabolic enzymes identified in our study may in turnbe useful targets for future pharmaceutical interventionsto reduce clinical side effects following propranolol treatment.