Bateman Emma, Venning Michael, Mirtschin Peter, Woods Anthony
Sansom Institute, School of Pharmacy and Medical Sciences, City East Campus, University of South Australia, GPO Box 2471, Adelaide, South Australia 5001.
J Venom Res. 2013 Oct 19;4:21-30. eCollection 2013.
The effects of various viperid and elapid venoms on the cellular biology of tumour-associated microvascular endothelial cells (TAMECs) were determined in the current study using cells isolated from a rat mammary adenocarcinoma. Previous studies to determine the effects of snake venoms on endothelial cells in vitro have in the main been performed on either human umbilical vein endothelial cells (HUVECs), bovine aortic endothelial cells (BAECs) or endothelial cell lines. These cell populations are accessible and easy to maintain in culture, however, it is well established that endothelial cells display vast heterogeneity depending upon the local microenvironment of the tissue from which they are isolated. Vascular targeting agents have been isolated from a variety of snake venoms, particularly from snakes of the Viperidae family, but it is yet to be established to what extent the venoms from Australian elapids possess similar vascular targeting properties. The present study used endothelial cells (ECs) isolated from the microvasculature of a rat mammary adenocarcinoma to determine the effects of a panel of snake venoms, including viperid venoms with known apoptotic activity and elapid venoms (both exotic and indigenous to Australia), on endothelial morphology and viability, paying specific attention to apoptotic responses. Three of the five Australian snake venoms investigated in this study elicited significant apoptotic responses in ECs which were in many ways similar to responses elicited by the selected viperid venoms. This suggests that these Australian elapids may possess vascular targeting components similar to those found within viperid venoms.
在本研究中,使用从大鼠乳腺腺癌分离的细胞,测定了各种蝰蛇科和眼镜蛇科毒液对肿瘤相关微血管内皮细胞(TAMECs)细胞生物学的影响。以往关于蛇毒对体外内皮细胞作用的研究主要是在人脐静脉内皮细胞(HUVECs)、牛主动脉内皮细胞(BAECs)或内皮细胞系上进行的。这些细胞群体容易获取且易于在培养中维持,然而,众所周知,内皮细胞根据其分离组织的局部微环境表现出巨大的异质性。血管靶向剂已从多种蛇毒中分离出来,特别是从蝰蛇科的蛇中,但澳大利亚眼镜蛇科毒液在多大程度上具有类似的血管靶向特性尚待确定。本研究使用从大鼠乳腺腺癌微血管分离的内皮细胞(ECs),来测定一组蛇毒的作用,包括具有已知凋亡活性的蝰蛇科毒液和眼镜蛇科毒液(既有来自澳大利亚以外的,也有澳大利亚本土的),对内皮细胞形态和活力的影响,并特别关注凋亡反应。本研究中所研究的五种澳大利亚蛇毒中有三种在ECs中引发了显著的凋亡反应,这些反应在许多方面与所选蝰蛇科毒液引发的反应相似。这表明这些澳大利亚眼镜蛇科蛇可能具有与蝰蛇科毒液中发现的类似的血管靶向成分。