Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells
Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells
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DOI：
10.1038/sj.jcbfm.9600395
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发表时间：
2007-05-01
影响因子：
6.3
通讯作者：
Hallenbeck, John M.
中科院分区：
文献类型：
--
作者：
Lee, Yang-ja;Miyake, Shin-ichi;Hallenbeck, John M.
冬眠麻木提供了一个极好的自然模型，可以耐受大脑和其他器官的血流量大幅减少。在这里，我们报告说，在13线地松鼠的麻痹，大量的SUMO化发生在大脑，肝脏和肾脏。小泛素相关修饰物（SUMO）结合的水平与Ubc 9（SUMO特异性E2结合酶）的表达水平一致。单独的低温也增加了SUMO结合，但不像冬眠迟钝那么明显。增加SUMO结合（由Ubc 9过表达、缺血预处理（PC）+/-低温诱导）对于SHSY 5 Y神经母细胞瘤细胞对氧/葡萄糖剥夺（OGD）的耐受性是必要的和充分的（“体外缺血”）;减少SUMO结合（由显性负性Ubc 9诱导）严重降低这些细胞对OGD的耐受性。这些数据表明，SUMO化的蛋白质的翻译后修饰是冬眠迟钝的一个突出特征，并且对于经受OGD的SHSY 5 Y细胞中缺血PC +/-低温的细胞保护是至关重要的。
Hibernation torpor provides an excellent natural model of tolerance to profound reductions in blood flow to the brain and other organs. Here, we report that during torpor of 13-lined ground squirrels, massive SUMOylation occurs in the brain, liver, and kidney. The level of small ubiquitin-related modifier ( SUMO) conjugation coincides with the expression level of Ubc9, the SUMO specific E2-conjugating enzyme. Hypothermia alone also increased SUMO conjugation, but not as markedly as hibernation torpor. Increased SUMO conjugation ( induced by Ubc9 overexpression, ischemic preconditioning ( PC)+/- hypothermia) was necessary and sufficient for tolerance of SHSY5Y neuroblastoma cells to oxygen/ glucose deprivation (OGD) (' in vitro ischemia'); decreased SUMO conjugation (induced by a dominant-negative Ubc9) severely reduced tolerance to OGD in these cells. These data indicate that post-translational modification of proteins by SUMOylation is a prominent feature of hibernation torpor and is critical for cytoprotection by ischemic PC +/- hypothermia in SHSY5Y cells subjected to OGD.