Calpain is involved in cisplatin-induced endothelial injury in an in vitro three-dimensional blood vessel model
Calpain is involved in cisplatin-induced endothelial injury in an in vitro three-dimensional blood vessel model
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DOI：
10.3892/ijo_00000780
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发表时间：
2010-11-01
影响因子：
5.2
通讯作者：
Nakano, Takashi
中科院分区：
文献类型：
--
作者：
Eguchi, Ryoji;Fujimori, Yoshihiro;Nakano, Takashi
研究内皮细胞的体外损伤。我们建立了三维（3-D）血管模型，其中人脐静脉内皮细胞在碱性成纤维细胞生长因子和血管内皮生长因子存在下生长。然后，我们对顺铂进行了比较研究（顺铂-二氨-二氯。CDDP）诱导的内皮损伤。在三维培养中，CDDP诱导细胞死亡和管破裂没有DNA损伤，而CDDP诱导细胞凋亡伴随着DNA损伤的单层培养。CDDP也诱导caspase-3的激活在两种文化中的浓度依赖性的方式。一种广谱的半胱天冬酶抑制剂，zVAD-fastin，未能防止CDDP诱导的细胞死亡和管破裂在3-D培养，而zVAD-fastin抑制CDDP诱导的细胞凋亡在单层培养。钙蛋白酶抑制剂。MDL 28170在3-D培养中减弱CDDP诱导的细胞死亡和管破裂，但在单层培养中不减弱细胞凋亡。这些结果表明，钙蛋白酶参与CDDP诱导的内皮细胞损伤的3-D培养和有显着差异的信号通路之间的3-D和单层培养。
To study endothelial injury in vitro. we established a three-dimensional (3-D) blood vessel model in which human umbilical vein endothelial cells were grown in the presence of basic fibroblast growth factor and vascular endothelial growth factor. We then performed comparative studies on cisplatin (cis-platinum-diammine-dichloride. CDDP)-induced endothelial injury in 3-D and monolayer cultures. In 3-D culture, CDDP induced cell death and tube breakdown without DNA damage, whereas CDDP induced apoptosis accompanied by DNA damage in monolayer culture. CDDP also induced caspase-3 activation in a concentration-dependent manner in both cultures. A broad-spectrum caspase inhibitor, zVAD-fmk, failed to prevent CDDP-induced cell death and tube breakdown in 3-D culture, whereas zVAD-fmk suppressed CDDP-induced apoptosis in monolayer culture. A calpain inhibitor. MDL28170, attenuated CDDP-induced cell death and tube breakdown in 3-D culture, but not apoptosis in monolayer culture. These results showed that calpain is involved in CDDP-induced endothelial injury in 3-D culture and there are significant differences in signaling pathways between 3-D and monolayer cultures.