title: Enantioselective pharmacodynamics of propranolol in HUVEC cells: a study using chiral 2D gel electrophoresis and mass spectrometry.
abstract: Propranolol (PRO), a nonselective β-adrenergic receptor (β-AR) antagonist, has two enantiomers, R(+)-PRO and S(-)-PRO, which have diverse biological effects. For example, S(-)-PRO blocks the β-receptor ~100 times more strongly than R(+)-PRO. However, the signaling pathway that causes this difference remains unclear. This pathway may affect the expression of numerous proteins, some of which play key roles during the drug action process. Therefore, we treated human umbilical vein endothelial cells (HUVECs) with R(+)-PRO and S(-)-PRO in order to identify differentially expressed proteins and to determine their functions in the drug action process. Of the 22 differentially expressed protein spots investigated, 14 demonstrated higher expression levels in the R(+)-PRO-treated cells, while 8 demonstrated lower expression levels in the same cells. Mass spectrometry identified 10 of the differentially expressed proteins: 4 signaling molecules, 2 metabolic enzymes, 3 heat shock proteins and 1 cytoskeleton protein. Our results suggest that these differentially expressed proteins, particularly guanine nucleotide-binding protein subunit β-2-like 1 (GBLP), are the key biomacromolecules underlying the mechanism by which PRO enantiomers induce stereoselective cellular responses. The results aid in clarifying the role of PRO in the treatment of arrhythmia and angina.
authors: Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, PR China.
authors: Xiaoqin
authors: X
authors: Mao
authors: Xiongfei
authors: X
authors: Jia
authors: Feng
authors: F
authors: Qiu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D011433:Propranolol / Q000494:pharmacology*; D020543:Proteome; D040901:Proteomics / Q000379:methods
chemical_list: D000319:Adrenergic beta-Antagonists; D044387:GTP-Binding Protein beta Subunits; D020543:Proteome; D011433:Propranolol