Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model.
Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model.
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DOI：
10.3390/cells10040906
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发表时间：
2021-04-14
期刊：
影响因子：
6
通讯作者：
Hardiman G
中科院分区：
文献类型：
--
作者：
Cahill T;da Silveira WA;Renaud L;Williamson T;Wang H;Chung D;Overton I;Chan SSL;Hardiman G
以重返月球为目标的Artemis方案的发展正在推动技术进步，最终将把人类带到火星，并预示着行星际空间旅行的新时代。然而，长期太空旅行带来了独特的挑战，包括暴露于银河宇宙射线和潜在太阳粒子事件的电离辐射，暴露于微重力以及独立于地球的探索所带来的特定营养挑战。电离辐射是未来太空旅行面临的主要障碍之一，因为它会产生氧化应激并直接损伤细胞结构，如DNA，从而导致基因组不稳定，端粒缩短，细胞外基质重塑和持续炎症。在胃肠道（GIT）中，这可能导致漏肠综合征，穿孔和动力问题，影响GIT功能并影响营养状况。虽然目前的对策，如航天器屏蔽可以减弱有害的生物效应，但它们会产生有害的次级粒子，导致辐射照射。我们假设，诱导的torpor-like状态将赋予辐射防护作用的证据表明，冬眠延长辐射松鼠的生存时间相比，积极控制。为了验证这一假设，一个torpor-like状态诱导斑马鱼使用褪黑激素治疗和降低温度，辐射暴露在10天的过程中进行了两次。通过从GIT提取的mRNA的RNA测序和qPCR评估诱导性麻痹的保护作用。对转录组数据进行通路和网络分析，以确定辐射、休眠和休眠+辐射组中的基因组特征。表型分析表明，褪黑激素和降低温度成功地诱导了一个torpor-like状态在斑马鱼所示的代谢和活动水平下降。基因组分析表明，低剂量辐射造成DNA损伤和氧化应激，引发应激反应，包括类固醇信号传导和代谢变化以及细胞周期停滞。Torpor通过增加促生存信号减弱应激反应，通过氧效应减少氧化应激，检测和去除错误折叠的蛋白质。这个概念验证模型提供了令人信服的初步证据，利用诱导torpor-like状态作为辐射暴露的潜在对策。
The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. In the gastrointestinal tract (GIT) this can lead to leaky gut syndrome, perforations and motility issues, which impact GIT functionality and affect nutritional status. While current countermeasures such as shielding from the spacecraft can attenuate harmful biological effects, they produce harmful secondary particles that contribute to radiation exposure. We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and reduced temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing and qPCR of mRNA extracted from the GIT. Pathway and network analysis were performed on the transcriptomic data to characterise the genomic signatures in radiation, torpor and torpor + radiation groups. Phenotypic analyses revealed that melatonin and reduced temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Genomic analyses indicated that low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, and cell cycle arrest. Torpor attenuated the stress response through an increase in pro-survival signals, reduced oxidative stress via the oxygen effect and detection and removal of misfolded proteins. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.4
作者：
Chylack, Leo T., Jr.;Peterson, Leif E.;Cucinotta, Francis A.
通讯作者：
Cucinotta, Francis A.
影响因子：
16.6
作者：
Acedo, Joaquin Navajas;Voas, Matthew G.;Piotrowski, Tatjana
通讯作者：
Piotrowski, Tatjana
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1073/pnas.0802432105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Chen, Zuozhou;Cheng, C. -H. Christina;Chen, Liangbiao
通讯作者：
Chen, Liangbiao