title: Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells.
abstract: β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M3 receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury.
authors.affiliation: Wuhan University, Zhongnan Hospital, Department of Anesthesiology, WuhanHubei, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Huazhong University of Science and Technology, Department of Osteology, Pu Ai Hospital, WuhanHubei, China.
authors.forename: F
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Wuhan University, Zhongnan Hospital, Department of Anesthesiology, WuhanHubei, China.
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Zhang
authors.affiliation: Wuhan University, Zhongnan Hospital, Department of Anesthesiology, WuhanHubei, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Wuhan University, Zhongnan Hospital, Department of Anesthesiology, WuhanHubei, China.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.affiliation: Wuhan University, Zhongnan Hospital, Department of Anesthesiology, WuhanHubei, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Wang