β cell cytoprotection using lentiviral vector-based iNOS-specific shRNA delivery
β cell cytoprotection using lentiviral vector-based iNOS-specific shRNA delivery
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DOI：
10.1016/j.bbrc.2007.03.115
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发表时间：
2007-05-25
影响因子：
3.1
通讯作者：
O'Brien, Timothy
中科院分区：
文献类型：
--
作者：
McCabe, Cillian;O'Brien, Timothy
细胞因子诱导的β细胞病理生理学的特征在于诱导iNOS表达。iNOS表达的抑制保护β细胞免受精氨酸介导的破坏。能够稳定抑制iNOS表达的基于载体的shRNA策略的开发可能提供保护β细胞免受细胞因子毒性的新平台。在这份报告中，慢病毒shRNA载体沉默iNOS表达的效用进行了评估，胰岛素瘤细胞活力，诱导iNOS表达和积累的亚硝酸盐在奎宁诱导的β细胞毒性模型。在这里，我们首次报道了使用基于慢病毒载体的shRNA递送来有效地抑制IL-1 β介导的iNOS表达诱导、亚硝酸盐的积累，并提供针对IL-1 β暴露的细胞毒性作用的显著保护。此外，未发生内源性β细胞nNOS的非特异性敲低。(c)2007 Elsevier Inc保留所有权利。
Cytokine-induced beta cell pathophysiology is characterised by the induction of iNOS expression. Inhibition of iNOS expression protects beta cells from cytokine-mediated destruction. The development of vector-based shRNA strategies capable of stably suppressing iNOS expression may provide a novel platform to protect beta cells from cytokine toxicity. In this report the utility of lentiviral shRNA vectors to silence iNOS expression was evaluated with respect to insulinoma cell viability, the induction of iNOS expression and the accumulation of nitrite in a cytokine-induced beta cell toxicity model. Here, we report for the first time on the use of lentiviral vector-based shRNA delivery to efficiently suppress the IL-1 beta-mediated induction of iNOS expression, the accumulation of nitrite and provide significant protection against the cytotoxic effects of IL-1 beta exposure. Moreover, non-specific knockdown of endogenous beta cell nNOS did not occur. (c) 2007 Elsevier Inc All rights reserved.