title: Penehyclidine hydrochloride attenuates LPS-induced iNOS production by inhibiting p38 MAPK activation in endothelial cells.
abstract: The aim of this study was to investigate the inhibitory effect of penehyclidine hydrochloride (PHC) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production in human endothelial cell. Cultured endothelial cells were pretreated with PHC, followed by LPS treatment. NO activity were determined. iNOS expression and p38 mitogen-activated protein kinase (p38 MAPK) protein expression were measured by Western blot analysis. LPS treatment significantly induced p38 MAPK activation, iNOS expression, and NO production, which could be attenuated by 2 μg/ml PHC pretreatment. Furthermore, our study showed LPS-induced NO production and iNOS expression were suppressed by p38 MAPK inhibitor SB203580 pretreatment. We concluded that PHC attenuates NO production and iNOS expression by suppressing the activation of p38 MAPK pathway, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced endothelial cell injury.
authors: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, People's Republic of China.
authors: Jia
authors: J
authors: Zhan
authors: Zong-Ze
authors: ZZ
authors: Zhang
authors: Chang
authors: C
authors: Chen
authors: Kai
authors: K
authors: Chen
authors: Yan-Lin
authors: YL
authors: Wang
references: Cytokine. 2008 Mar;41(3):279-85
references: 18206384
references: Crit Care Med. 2001 Jul;29(7 Suppl):S21-7
references: 11445730
references: Mol Biol Rep. 2010 Dec;37(8):3801-12
references: 20224909
references: J Physiol Pharmacol. 2003 Dec;54(4):469-87
references: 14726604
references: Life Sci. 2005 Nov 26;78(2):210-23
references: 16154160
references: Mol Biol Rep. 2011 Mar;38(3):1909-14
references: 20845074
references: Mol Cell Biochem. 2004 Jul;262(1-2):51-9
references: 15532709
references: Biochem Biophys Res Commun. 2005 Jun 17;331(4):1421-8
references: 15883033
references: Pharmacol Res. 2009 Oct;60(4):296-302
references: 19386282
references: Cell Res. 2005 Jan;15(1):11-8
references: 15686620
references: Cell Signal. 2000 Jan;12(1):1-13
references: 10676842
references: Mol Biol Rep. 2006 Dec;33(4):287-94
references: 17089209
references: Pharmacol Res. 2004 May;49(5):433-9
references: 14998552
references: Chirurg. 2002 Nov;73(11):1093-9
references: 12430059
references: Chin J Traumatol. 2010 Feb;13(1):15-9
references: 20109362
references: Eur J Anaesthesiol. 2010 Sep;27(9):824-8
references: 20523213
references: FEBS Lett. 2006 Sep 18;580(21):4984-90
references: 16949582
references: J Endotoxin Res. 2003;9(2):108-12
references: 12803884
references: Lab Invest. 2006 Jan;86(1):9-22
references: 16357866
references: Curr Top Med Chem. 2005;5(10):921-8
references: 16178737
references: Mol Biol Rep. 2011 Aug;38(6):3615-22
references: 21110116
references: Mol Biol Rep. 2011 Apr;38(4):2301-6
references: 21052844