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蝰蛇、蝰蛇和虎蛇蛇毒中的 PLA2-s 与血小板、细菌和癌细胞的相互作用。

Interactions of PLA2-s from Vipera lebetina, Vipera berus berus and Naja naja oxiana venom with platelets, bacterial and cancer cells.

机构信息

National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.

出版信息

Toxins (Basel). 2013 Jan 24;5(2):203-23. doi: 10.3390/toxins5020203.

Abstract

Secretory phospholipasesA(2) (sPLA(2)s) form a large family of structurally related enzymes widespread in nature. Herein, we studied the inhibitory effects of sPLA(2)s from Vipera lebetina (VLPLA(2)), Vipera berus berus (VBBPLA(2)), and Naja naja oxiana (NNOPLA(2)) venoms on (i) human platelets, (ii) four different bacterial strains (gram-negative Escherichia coli and Vibrio fischeri; gram-positive Staphylococcus aureus and Bacillus subtilis) and (iii) five types of cancer cells (PC-3, LNCaP, MCF-7, K-562 and B16-F10) in vitro. sPLA(2)s inhibited collagen-induced platelet aggregation: VBBPLA(2) IC(50) = 0.054, VLPLA(2) IC(50) = 0.072, NNOPLA(2) IC(50) = 0.814 μM. p-Bromophenacylbromide-inhibited sPLA(2) had no inhibitory action on platelets. 36.17 μM VBBPLA(2 )completely inhibited the growth of gram-positive Bacillus subtilis whereas no growth inhibition was observed towards gram-negative Escherichia coli. The inhibitory action of sPLA(2)s (~0.7 μM and ~7 μM) towards cancer cells depended on both venom and cell type. VBBPLA(2 )(7.2 μM) inhibited significantly the viability of K-562 cells and the cell death appeared apoptotic. The sPLA(2)s exhibited no inhibitory effect towards LNCaP cells and some effect (8%-20%) towards other cells. Thus, already sub-μM concentrations of sPLA(2)s inhibited collagen-induced platelet aggregation and from the current suite of studied svPLA(2)s and test cells, VBBPLA(2) was the most growth inhibitory towards Bacillus subtilis and K-562 cells.

摘要

分泌型磷脂酶 A2(sPLA2s)构成了一个广泛存在于自然界中的结构相关酶的大家族。在此,我们研究了来自蝰蛇(VLPLA2)、蝰蛇(VBBPLA2)和眼镜蛇(NNOPLA2)毒液的 sPLA2s 对(i)人血小板、(ii)四种不同的细菌菌株(革兰氏阴性大肠杆菌和发光弧菌;革兰氏阳性金黄色葡萄球菌和枯草芽孢杆菌)和(iii)五种类型的癌细胞(PC-3、LNCaP、MCF-7、K-562 和 B16-F10)的体外抑制作用。sPLA2s 抑制胶原诱导的血小板聚集:VBBPLA2 IC50 = 0.054,VLPLA2 IC50 = 0.072,NNOPLA2 IC50 = 0.814 μM。p-溴苯乙酰溴抑制的 sPLA2 对血小板没有抑制作用。36.17 μM 的 VBBPLA2 完全抑制革兰氏阳性枯草芽孢杆菌的生长,而对革兰氏阴性大肠杆菌没有观察到生长抑制。sPLA2s(0.7 μM 和7 μM)对癌细胞的抑制作用取决于毒液和细胞类型。VBBPLA2(7.2 μM)显著抑制 K-562 细胞的活力,细胞死亡呈凋亡。sPLA2s 对 LNCaP 细胞没有抑制作用,对其他细胞有一定的作用(8%-20%)。因此,已经亚微摩尔浓度的 sPLA2s 抑制胶原诱导的血小板聚集,在所研究的 svPLA2s 和测试细胞中,VBBPLA2 对枯草芽孢杆菌和 K-562 细胞的生长抑制作用最强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa6c/3640532/84b785afe463/toxins-05-00203-g001.jpg

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