Enantioselective pharmacodynamics of propranolol in HUVEC cells: A study using chiral 2D gel electrophoresis and mass spectrometry

Mao,Xiaoqin; Jia,Xiongfei; Qiu,Feng

doi:10.3892/mmr.2013.1464

Enantioselective pharmacodynamics of propranolol in HUVEC cells: A study using chiral 2D gel electrophoresis and mass spectrometry

Authors:
- Xiaoqin Mao
- Xiongfei Jia
- Feng Qiu
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Affiliations: Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China, Department of Clinical Laboratory, Kunming General Hospital, Kunming, Yunnan 650032, P.R. China, Department of Pharmacy, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: May 8, 2013 https://doi.org/10.3892/mmr.2013.1464
Pages: 128-132

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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.

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1	Steiner S and Anderson NL: Pharmaceutical proteomics. Ann NY Acad Sci. 919:48–51. 2000. View Article : Google Scholar
2	Graves PR, Kwiek JJ, Fadden P, et al: Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol Pharmacol. 62:1364–1372. 2002. View Article : Google Scholar : PubMed/NCBI
3	Bruneau JM, Maillet J, Tagat E, et al: Drug induced protome changes in Candida albicans: comparison of the effect of beta(1,3) glucan synthase inhibitors and two triazoles, fluconazole and itraconazole. Proteomics. 3:325–336. 2003.PubMed/NCBI
4	You QD and Lin GQ: Chiral Drugs: Research and Application. 34. Chemical Industry Press; Beijing: pp. 230–234. 2003
5	Lee DH, Jacobs DR Jr, Gross M, et al: Gamma-glutamyltransferase is a predictor of incident diabetes and hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Clin Chem. 49:1358–1366. 2003. View Article : Google Scholar : PubMed/NCBI
6	Lee DH, Ha MH, Kim JH, et al: Gamma-glutamyltransferase and diabetes - a 4 years follow-up study. Diabetologia. 46:359–364. 2003.PubMed/NCBI
7	Dorsch M, Danial NN, Rothman PB and Goff SP: A thrombopoietin receptor mutant deficient in Jak-STAT activation mediates proliferation but not differentiation in UT-7 cells. Blood. 94:2676–2685. 1999.PubMed/NCBI
8	Guil S, de La Iglesia N, Fernández-Larrea J, et al: Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm and nucleus. Cancer Res. 63:5178–5187. 2003.PubMed/NCBI
9	Kim IS, Ryang YS, Kim YS, et al: Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKC delta/Ras cascades in HOS cells. Life Sci. 73:447–459. 2003. View Article : Google Scholar : PubMed/NCBI
10	Mochly-Rosen D, Khaner H and Lopez J: Identification of intracellular receptor proteins for activated protein kinase C. Proc Natl Acad Sci USA. 88:3997–4000. 1991. View Article : Google Scholar : PubMed/NCBI
11	Mamidipudi V, Dhillon NK, Parman T, Miller LD, Lee KC and Cartwright CA: RACK1 inhibits colonic cell growth by regulating Src activity at cell cycle checkpoints. Oncogene. 26:2914–2924. 2007. View Article : Google Scholar : PubMed/NCBI
12	Bolger GB, Baillie GS, Li X, et al: Scanning peptide array analyses identify overlapping binding sites for the signaling scaffold proteins, beta-arrestin and RACK1, in cAMP-specific phosphodiesterase PDE4D5. Biochem J. 398:23–36. 2006. View Article : Google Scholar
13	Kiely PA, O'Gorman D, Luong K, Ron D and O'Connor R: Insulin-like growth factor I controls a mutually exclusive association of RACK1 with protein phosphatase 2A and beta1 integrin to promote cell migration. Mol Cell Biol. 26:4041–4051. 2006. View Article : Google Scholar : PubMed/NCBI
14	Hermanto V, Zong CS, Li W and Wang LH: RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 22:2345–2365. 2002. View Article : Google Scholar
15	Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A and Ron D: NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proc Natl Acad Sci USA. 99:5710–5715. 2002. View Article : Google Scholar : PubMed/NCBI
16	Battaini F, Pascale A, Paoletti R and Govoni S: The role of anchoring protein RACK1 in PKC activation in the ageing rat brain. Trends Neurosci. 20:410–415. 1997. View Article : Google Scholar : PubMed/NCBI
17	Qiu Y, Mao T, Zhang Y, et al: A crucial role for RACK1 in the regulation of glucose-stimulated IRE1alpha activation in pancreatic beta cells. Sci Signal. 3:ra72010.PubMed/NCBI
18	Patterson RL, van Rossum DB, Barrow RK and Snyder SH: RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca²⁺ release. Proc Natl Acad Sci USA. 101:2328–2332. 2004. View Article : Google Scholar : PubMed/NCBI