Molecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and Tibetans

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Title:	Molecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and Tibetans
Authors:	Lu, HF;Shih, MC;Hsueh, SC;Chen, CM;Chang, JY;Chang, JG
Contributors:	附設醫院醫研部;China Med Univ Hosp, Dept Mol Med, Taichung 404, Taiwan;China Med Univ Hosp, Dept Lab Med, Taichung, Taiwan;Cheng Hsin Rehabil & Med Ctr, Dept Clin Pathol, Taipei, Taiwan;Fu Jen Catholic Univ, Coll Human Ecol, Taipei, Taiwan;Taipei Inst Pathol, Taipei, Taiwan;Taichung Healthcare & Management Univ, Dept Biol Sci & Technol, Taichung, Taiwan
Date:	2005
Issue Date:	2010-09-24 15:00:37 (UTC+8)
Publisher:	BLACKWELL PUBLISHING
Abstract:	5-[4-Acridin-9-ylamino]phenyl]-5-methyl-3-methylenedihydrofuran-2-one (CYL-26z) inhibited the formyl-Met-Leu-Phe (fMLP)stimulated phospholipase D (PLD) activity, which was assessed by the production of phosphatidylethanol (PEt) in the presence of ethanol, in rat neutrophils (IC50 1.2 +/- 0.2 mu M). CYL-26z caused a slight but significant attenuation of the global protein tyrosine phosphorylation stimulated by fMLP only at concentrations of CYL-26z up to 30 mu M. CYL-26z blocked the membrane recruitment of protein kinase C-alpha (PKC-alpha) at concentrations of CYL-26z >= 3 mu M, but failed to affect the membrane association of PKC-beta I and -beta II. The translocation of RhoA to the membrane was attenuated by CTP gamma S (IC50 3.8 +/- 0.8 mu M) in fMLP-stimulated neutrophils, whereas CYL-26z caused no significant inhibition of the membrane recruitment of ADP-ribosylation factor (Arf). CYL-26z inhibited the activation of RhoA and dissociation of the RhoA-Rho guanine nucleotide dissociation inhibitor (GDI) complex in fMLP-stimulated neutrophils (IC50 1.8 +/- 1.0 mu M and 1.8 +/- 0.9 mu M, respectively). In a cell-free system, CYL-26z effectively attenuated the membrane association of RhoA in response to GTP gamma S (IC50 1.3 +/- 0.5 mu M). In contrast, the GTP gamma S-stimulated translocation of Arf to membrane was suppressed only at concentrations of CYL-26z up to 30 mu M. CYL-26z inhibited the fMLP-stimulated membrane expression of CD11b, CD45 and CD63, and the release of lysozyme and beta-glucuronidase. These results indicate that CYL-26z inhibited the fMLP-stimulated PLD activity, mainly through the blockade of RhoA activation, and degranulation in rat neutrophils. (c) 2005 Elsevier Inc. All rights reserved.
Relation:	JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS 30(5):491-496
Appears in Collections:	[China Medical University Hospital] Jurnal articles

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