Comparative proteomic analysis of extracellular proteins reveals secretion of T-kininogen from vascular smooth muscle cells in response to incubation with s-enantiomer of propranolol.
Propranolol, a nonselective beta blocker, exerts blocking activity both on beta1 adrenoceptors and beta2 ones, with the S-enantiomer being more active than the R-enantiomer. The aim of the study was to investigate the secreted proteins with differential protein expression levels in culture medium of vascular smooth muscle cells (A7r5) incubated separately with individual enantiomers of propranolol using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional LC-MS/MS approach. Our results indicated that secretion of T-kininogen by S-enantiomer of propranolol incubated cells was greatly enhanced as compared with that of R-enantiomer incubated cells or control cells. It can be inferred that the S-enantiomer of propranolol will induce more Ile-Ser-bradykinin (BK) (T-kinin), the vasoactive peptides. This therefore provides molecular evidence and possible link of T-kininogen with treatment of cardiovascular disease associated with propranolol treatment.
School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University, Singapore.
Jianjun
J
Sui
Jianhua
J
Zhang
Chi Bun
CB
Ching
Wei Ning
WN
Chen
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D045604:Extracellular Fluid / Q000737:chemistry*; D007704:Kininogens / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry / Q000494:pharmacology*; D040901:Proteomics; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D007704:Kininogens; D010455:Peptides; D011433:Propranolol