The cryoprotectant trehalose could inhibit ERS-induced apoptosis by activating autophagy in cryoprotected rat valves.
The cryoprotectant trehalose could inhibit ERS-induced apoptosis by activating autophagy in cryoprotected rat valves.
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DOI：
10.1371/journal.pone.0194078
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Chang Q
中科院分区：
文献类型：
--
作者：
Wu H;Chang Q
瓣膜疾病是与高发病率和死亡率密切相关的常见健康问题;主动脉瓣同种异体移植可能是提高生存率和缓解症状的有希望的方法。然而，常用的瓣膜冷冻保存方法尚未观察到理想的组织活力，这可能导致冷冻保存组织的凋亡和坏死。已观察到海藻糖通过维持细胞结构和保护细胞免受应激反应而发挥积极作用。在这项研究中，我们研究了海藻糖在保护大鼠瓣膜组织免受冷却过程的影响。我们发现，在冷冻保存过程中，用海藻糖处理的大鼠瓣膜的细胞功能比用二甲基亚砜（DMSO）处理的瓣膜的细胞功能更高。为了进一步探讨其机制，我们发现海藻糖可以下调参与细胞凋亡的重要分子caspase-3的表达。此外，海藻糖处理还降低了内质网应激（ERS）过程中的关键蛋白-葡萄糖调节蛋白78（GRP 78）和CCAAT/增强子结合蛋白同源蛋白（CHOP）。有趣的是，我们观察到海藻糖通过mTOR非依赖性但p38 MAPK依赖性信号通路促进冷冻保护的大鼠瓣膜细胞自噬。此外，miR-221和miR-32与这些细胞活性有关。总之，我们的研究为同种异体瓣膜的保存提供了一种新的有意义的低温保存方法。
Valvular diseases are common health problems that are strongly related to high morbidity and mortality; aortic valve allograft transplantation may be a promising way to improve survival and relieve symptoms. However, ideal tissue viability has not been observed with common valve cryopreservation methods, which could lead to apoptosis and necrosis in cryopreserved tissue. It has been observed that trehalose plays a positive role by acting to maintain cell structures and protect cells from stress responses. In this study, we studied the effects of trehalose in protecting rat valve tissue from the cooling process. We found improved higher cell function in rat valves treated with trehalose during cryopreservation than in those treated with dimethyl sulphoxide (DMSO). To further explore the mechanisms, we found that trehalose could down-regulate the expression of cleaved caspase-3, an important molecule involved in cell apoptosis. In addition, treatment with trehalose also decreased Glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP), the key proteins in the endoplasmic reticulum stress (ERS) process. Intriguingly, we observed that trehalose promotes cryoprotected rat valve cell autophagy via an mTOR-independent but p38 MAPK-dependent signaling pathway. Additionally, miR-221 and miR-32 have been implicated in such cell activities. In summary, our study offers a new and meaningful cryopreservation approach for valve allograft storage.
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影响因子：
0.9
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