Background
PAF(C16) is a membrane-derived phospholipid, It is also a platelet activating factor and a ligand for PAF G protein-coupled receptor (PAFR). PAF(C16) is a potent MAPK and MEK/ERK activator. PAF(C16) can induce cell exosmosis in a dose-dependent manner and improve vascular permeability. PAF(C16) inhibits Caspase-dependent cell apoptosis by activating PAFR and has anti-apoptotic effect[1-4].
PAF(C16) (10, 25, 50, and 100 μg/ml; 2 h) inhibits M. smegmatis and M. bovis BCG growth in a dose-dependent manner[2]. PAF(C16) (10 nM; 24 h) can destroy the decreased levels of IL-25 and IL-33 in cells caused by 5α-DHT [5]. 500 nM PAF(C16) increased the numbers of phenotypic Haematopoietic stem/progenitor cell (HSPC) and induced cell cycling of HSPC[6].
PAF(C16) (5 mg/kg; orally administrated every 3 days) significantly inhibited the effect of 5α-DHT on airway hyperreactivity (AHR) [4]. PAF(C16) (0.5-10 ng/kg) given as a bolus into the renal arterial circulation of pentobarbital sodium-anesthetized male Wistar rats caused systemic hypotension and produced a dose-dependent increase in renal blood flow [7].
参考文献:
[1]. Vadas, P, Perelman, B, et,al. Platelet-activating factor, histamine, and tryptase levels in human anaphylaxis. J. Allergy Clin. Immunol. 131, 144–149. doi: 10.1016/j.jaci.2012.08.016
[2]. Riaz MS, Kaur A, et,al. Direct Growth Inhibitory Effect of Platelet Activating Factor C-16 and Its Structural Analogs on Mycobacteria. Front Microbiol. 2018 Sep 11;9:1903. doi: 10.3389/fmicb.2018.01903. PMID: 30258409; PMCID: PMC6143801.
[3]. Ryan SD, Harris CS, et,al. Heterogeneity in the sn-1 carbon chain of platelet-activating factor glycerophospholipids determines pro- or anti-apoptotic signaling in primary neurons. J Lipid Res. 2008 Oct;49(10):2250-8. doi: 10.1194/jlr.M800263-JLR200. Epub 2008 Jun 12. PMID: 18550892.
[4]. B?gershausen N, Tsai IC, et,al. RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome. J Clin Invest. 2015 Sep;125(9):3585-99. doi: 10.1172/JCI80102. Epub 2015 Aug 17. PMID: 26280580; PMCID: PMC4588287.
[5]. Xia T, Ma J, et,al. Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221121320. doi: 10.1177/09603271221121320. PMID: 35982617.
[6]. Sun Q, Zhou Y, et,al. MEK1 activation enhances the ex vivo proliferation of haematopoietic stem/progenitor cell. Cell Biochem Funct. 2022 Jan;40(1):79-89. doi: 10.1002/cbf.3677. Epub 2021 Dec 2. PMID: 34855220.
[7]. Handa RK, Strandhoy JW, et,al. Platelet-activating factor is a renal vasodilator in the anesthetized rat. Am J Physiol. 1990 Jun;258(6 Pt 2):F1504-9. doi: 10.1152/ajprenal.1990.258.6.F1504. PMID: 2360650.
PAF(C16)是一种膜源磷脂，也是血小板活化因子和PAF G蛋白偶联受体(PAFR)的配体。PAF(C16)是一种有效的MAPK和MEK/ERK激活剂。PAF(C16)能以剂量依赖的方式诱导细胞外渗，改善血管通透性。PAF(C16)通过激活PAFR抑制caspase依赖性细胞凋亡，具有抗凋亡作用[1-4]。
PAF(C16) (10, 25, 50, and 100 μg/ml; 2 h)以剂量依赖的方式抑制耻垢分枝杆菌和牛分枝杆菌的生长[1]。PAF(C16) (10 nM ; 24 h)可破坏5α-DHT引起的细胞IL-25、IL-33水平下降[5]。500 nM PAF(C16)可增加表型造血干细胞/祖细胞(HSPC)的数量，并诱导HSPC的细胞周期[6]。
PAF(C16) (5 mg/kg; orally administrated every 3 days)显著抑制5α-DHT对气道高反应性(AHR)的影响[4]。给麻醉的雄性Wistar大鼠肾动脉循环注射PAF(C16) (0.5-10 ng/kg)可引起全体性低血压，并使肾血流量呈剂量依赖性增加[7]。
Protocol
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Cell experiment [1]:
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Cell lines
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BEAS-2B cells
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Preparation method
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Cells were divided into five groups, including control group, TGF-β1 treated group, TGF-β1 plus 5α-DHT treated group, TGF-β1 plus chicanine (a p38 MAPK and ERK1/2 inhibitor) treated group, TGF-β1 plus 5α-DHT and PAF(C16) treated group. The treated concentration and time of drugs were 1 nM 5α-DHT for 24 h, 50 μM chicanine for 24 h, 10 nM PAF(C16) for 24 h. Chicanine and PAF(C16) were dissolved in 2 % ethanol.
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Reaction Conditions
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10 nM; 24 h
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Applications
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PAF(C16) can destroy the decreased levels of IL-25 and IL-33 in cells caused by 5α-DHT.
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Animal experiment [1]:
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Animal models
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Female Wistar rats (220 ± 30 g)
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Preparation method
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The rats were randomly divided into six groups: control group, ovalbumin(OVA) model group (OVA), vehicle treated group (OVA + vehicle), 0.5 mg/kg 5α-DHT treated group (OVA + 5α-DHT), 15 mg/kg chicanine treated group (OVA + chicanine), 5α-DHT and 5 mg/kg PAF(C16) treated group (OVA +5α-DHT + PAF(C16)). During experiments, rats were orally administrated with vehicle or 5α-DHT or chicanine or 5α-DHT plus PAF(C16) every 3 days.
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Dosage form
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5 mg/kg; orally administrated every 3 days
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Applications
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PAF(C16) significantly inhibited the effect of 5α-DHT on airway hyperreactivity (AHR).
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参考文献:
[1]. Xia T, Ma J,et,al. Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221121320. doi: 10.1177/09603271221121320. PMID: 35982617.
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