Non-viral systemic delivery of siRNA or antisense oligonucleotides targeted to Jun N-terminal kinase 1 prevents cellular hypoxic damage.
Non-viral systemic delivery of siRNA or antisense oligonucleotides targeted to Jun N-terminal kinase 1 prevents cellular hypoxic damage.
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DOI：
10.1007/s13346-010-0003-1
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发表时间：
2011-02
影响因子：
5.4
通讯作者：
Minko, Tamara
中科院分区：
文献类型：
--
作者：
Betigeri, Seema;Zhang, Min;Garbuzenko, Olga;Minko, Tamara
关键词：
许多病理条件和环境影响导致严重的组织缺氧，加剧了原发疾病，引发细胞死亡，限制了患者的康复。我们假设抑制Jun氨基末端激酶1(JNK1)可以限制严重缺氧引起的组织损伤。为了验证这一假设，针对JNK1 mRNA的反义寡核苷酸(ASO)或小干扰RNA(SiRNA)分别被掺入或与中性或阳离子脂质体络合，并在低氧暴露前系统地给药。动物被放在一个特殊的房间里，房间里有空气(常氧)或含有6%O2和94%N2的混合气体(缺氧)。脂质体、ASO和siRNA被发现在肺、肾、脾和心脏中蓄积。在大脑中只发现了微量的脂质体及其有效载荷(ASO和siRNA)。JNK1蛋白的下调限制了缺氧条件下细胞死亡信号的激活、细胞的凋亡和组织的坏死损伤。因此，我们能够验证我们的假设，并提供了一种独特的方法的概念证据，通过抑制ASO或siRNA有效传递后的JNK1信号通路来防止细胞缺氧损伤。
Many pathological conditions and environmental impacts lead to the development of severe tissue hypoxia that aggravates the primary disorder, provokes cell death, and limits the patient’s recovery. We hypothesized that suppression of Jun N-terminal kinase 1 (JNK1) will limit tissue damage induced by severe hypoxia. To test the hypothesis, antisense oligonucleotides (ASO) or small interfering RNA (siRNA) targeted to JNK1 mRNA were incorporated or complexed with neutral or cationic liposomes, respectively, and administered systemically to mice prior to hypoxia exposure. The animals were placed in a special chamber ventilated with room air (normoxia) or a gas mixture containing 6% O2 and 94% N2 (hypoxia). Liposomes, ASO, and siRNA were found to accumulate in the lungs, kidney, spleen, and heart. Only trace amounts of liposomes and their payloads (ASO and siRNA) were found in the brain. The down regulation of JNK1 protein limited activation of cell death signal, apoptotic, and necrotic tissue damage under hypoxic conditions. Consequently, we were able to verify our hypothesis and provide proof of concept of a unique approach to the prevention of cellular hypoxic damage by the suppression of JNK1 signaling pathways after the efficient delivery of ASO or siRNA.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
2.5
作者：
Cho, Young-Eun;Ko, Jeong-Hun;Park, Jae-Hoon
通讯作者：
Park, Jae-Hoon
影响因子：
6.5
作者：
Blokhina, Olga;Fagerstedt, Kurt V.
通讯作者：
Fagerstedt, Kurt V.
DOI：
10.1073/pnas.0504274102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Dharap, SS;Wang, Y;Minko, T
通讯作者：
Minko, T
影响因子：
8
作者：
Cho, D.-H.;Lee, H.-J.;Jung, Y.-K.
通讯作者：
Jung, Y.-K.