Membrane proteomics of cellular responses to β-blocker carvedilol

Abstract

Carvedilol is a third generation β-blocker of multifaceted therapeutic potential. It is a non-selective antagonist of β1 and, β2 adrenoceptors and exhibits anti-α1–adrenergic activity. Clinically, carvedilol has been used in the treatment of congestive heart failure, ischemic heart disease and hypertension. However, the molecular mechanism behind the therapeutic effects of its individual enantiomers is not well understood. Previous study investigated the differential change of cytoplasmic proteins in cells incubated with individual enantiomers of carvedilol. Since membrane proteins play many important roles in the cells, profiling of membrane proteins may provide additional insights that were not obtained previously.

By performing membrane protein extraction using Mem-PER kit followed by analysis in iTRAQ coupled 2D-LC-MS/MS, a membrane protein profile of A7r5 cells treated separately with S- and R-carvedilol was established. 120 membrane proteins were identified with greater than 95% confidence level. Differential expression was identified in four of the proteins. The findings provide molecular explanation on the clinical effects related to carvedilol treatment. The established platform for profiling of membrane proteins may be applicable to future studies on other drugs.