首页> 外文期刊>Endothelium: Journal of endothelial cell research >Effects of first generation E1E3-deleted and second generation E1E3E4-deleted/modified adenovirus vectors on human endothelial cell death.
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Effects of first generation E1E3-deleted and second generation E1E3E4-deleted/modified adenovirus vectors on human endothelial cell death.

机译:第一代E1E3缺失和第二代E1E3E4缺失/修饰的腺病毒载体对人内皮细胞死亡的影响。

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摘要

Adenoviral vectors are promising tools for pulmonary vascular gene transfer. In first generation vectors, the viral E4 region is preserved (E4+ Ad), but E4 is deleted in second generation vectors (E4- Ad). These vectors were compared for their toxicity in human endothelial cells in terms of apoptosis and necrosis. Infection with E4+ Ad vectors reduced whereas E4- Ad vectors enhanced apoptosis under normal culture conditions. Furthermore, E4+ Ad protected against apoptosis induced by growth factor deprivation, while E4- Ad enhanced apoptosis triggered by ceramide. Ad vectors containing different E4 open reading frames, alone or in different combinations, showed similar effects to E4- Ad, leaving the viral genes that might be responsible for reducing apoptosis unidentified at the present time. As previously observed with E4+ Ad devoid of transgene, E4+ Ad carrying beta-galactosidase or green fluorescent protein under the control of either the RSV or CMV promoter also reduced apoptosis triggered by growth factor deprivation. In contrast, E4+ Ad containing a CFTR expression cassette did not reduce apoptosis, and E4- Ad with CFFR showed increased toxicity. We conclude that Ad vectors may have important effects on the control of apoptosis in transfected cells, depending on the residual expression of viral genes. This effect can be complicated by the action of transgene expression on cell survival.
机译:腺病毒载体是用于肺血管基因转移的有前途的工具。在第一代载体中,病毒的E4区域被保留(E4 + Ad),而第二代载体中的E4被删除(E4-Ad)。就细胞凋亡和坏死而言,比较了这些载体在人内皮细胞中的毒性。在正常培养条件下,E4 + Ad载体的感染减少,而E4-Ad载体的感染增加。此外,E4 + Ad可以防止生长因子剥夺诱导的细胞凋亡,而E4-Ad可以增强神经酰胺触发的细胞凋亡。单独或以不同组合包含不同E4开放阅读框的Ad载体显示出与E4-Ad相似的作用,目前尚不清楚可能负责减少细胞凋亡的病毒基因。如先前用不含转基因的E4 + Ad所观察到的那样,在RSV或CMV启动子的控制下携带β-半乳糖苷酶或绿色荧光蛋白的E4 + Ad也减少了由生长因子剥夺触发的凋亡。相反,含有CFTR表达盒的E4 + Ad不会减少细胞凋亡,而带有CFFR的E4-Ad则显示出增加的毒性。我们得出结论,取决于病毒基因的残留表达,Ad载体可能对转染细胞凋亡的控制有重要影响。转基因表达对细胞存活的作用可使这种作用变得复杂。

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