DNA-free recombinant SV40 capsids protect mice from acute renal failure by inducing stress response, survival pathway and apoptotic arrest.
DNA-free recombinant SV40 capsids protect mice from acute renal failure by inducing stress response, survival pathway and apoptotic arrest.
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DOI：
10.1371/journal.pone.0002998
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发表时间：
2008-08-20
期刊：
影响因子：
3.7
通讯作者：
Oppenheim, Ariella
中科院分区：
文献类型：
--
作者：
Butin-Israeli, Veronika;Uzi, Dotan;Abd-El-Latif, Mahmoud;Pizov, Galina;Eden, Arieh;Haviv, Yosef S.;Oppenheim, Ariella
病毒在感染期间诱导信号传导和宿主防御。利用这些自然触发机制来对抗器官或组织衰竭受到大多数病毒的有害影响的阻碍。在这里，我们证明了SV 40空衣壳（病毒样颗粒-VLP），没有DNA，诱导宿主HSP/c70和Akt-1生存途径，细胞生存机制的关键球员。我们推测这种信号可能会保护体内器官免受损伤。选择急性肾损伤（阿基）作为靶点。阿基是一种严重的人类常见疾病，由肾毒性药物、败血症或缺血通过肾小管细胞凋亡/坏死引起，具有高发病率和死亡率。VLP的全身给药在体内激活Akt-1并上调Hsp/c70。在汞诱导的阿基小鼠模型中的实验表明，在汞损伤之前用衣壳预处理显著减弱了细胞凋亡、氧化应激和毒性肾衰竭。存活率从12%增加到> 60%，具有广泛的剂量反应。这项研究表明，缺乏DNA的SV 40 VLP可能潜在地用作阿基的预防剂。我们预期，这些发现可能会预测到广泛的器官衰竭，使用空衣壳的SV 40以及其他病毒。
Viruses induce signaling and host defense during infection. Employing these natural trigger mechanisms to combat organ or tissue failure is hampered by harmful effects of most viruses. Here we demonstrate that SV40 empty capsids (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival pathways, key players in cellular survival mechanisms. We postulated that this signaling might protect against organ damage in vivo. Acute kidney injury (AKI) was chosen as target. AKI is critical, prevalent disorder in humans, caused by nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular cells, with high morbidity and mortality. Systemic administration of VLPs activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal failure were significantly attenuated by pretreatment with capsids prior to the mercury insult. Survival rate increased from 12% to >60%, with wide dose response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially be used as prophylactic agent for AKI. We anticipate that these finding may be projected to a wide range of organ failure, using empty capsids of SV40 as well as other viruses.
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DOI：
10.1083/jcb.107.4.1359
发表时间：
1988-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Haverty TP;Kelly CJ;Hines WH;Amenta PS;Watanabe M;Harper RA;Kefalides NA;Neilson EG
通讯作者：
Neilson EG
影响因子：
3.7
作者：
Mukherjee S;Abd-El-Latif M;Bronstein M;Ben-nun-Shaul O;Kler S;Oppenheim A
通讯作者：
Oppenheim A
影响因子：
7.3
作者：
Ignatov, A.;Robert, J.;Schaller, H. C.
通讯作者：
Schaller, H. C.
DOI：
10.1159/000086054
发表时间：
2005-01-01
期刊：
CELLULAR STRESS RESPONSES IN RENAL DISEASES
影响因子：
--
作者：
Kelly, KJ
通讯作者：
Kelly, KJ
影响因子：
64.5
作者：
Marsh M;Helenius A
通讯作者：
Helenius A