Sumo-2/3-ylation following in vitro modeled ischemia is reduced in delayed ischemic tolerance.
Sumo-2/3-ylation following in vitro modeled ischemia is reduced in delayed ischemic tolerance.
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DOI：
10.1016/j.brainres.2009.03.034
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发表时间：
2009-05-26
期刊：
影响因子：
2.9
通讯作者：
Meller R
中科院分区：
文献类型：
--
作者：
Loftus LT;Gala R;Yang T;Jessick VJ;Ashley MD;Ordonez AN;Thompson SJ;Simon RP;Meller R
最近的一些研究表明，sumo-2/3修饰的蛋白质发生在有害的缺血，然而，sumo-2/3-ylation也可能与冬眠介导的神经保护。在这里，我们研究了小泛素化的蛋白质缺血和缺血耐受使用我们建立的体外模型缺血（氧和葡萄糖剥夺; OGD）。在有害的缺血（120分钟OGD）后，我们观察到高分子量蛋白质（>85 kDa）的sumo-2/3-化显著增加，但蛋白质的sumo-1-化没有增加。当培养物在24小时前用无害的30分钟OGD预处理时，120分钟OGD后的Sumo-2/3-化减少（延迟缺血耐受）。然而，我们没有观察到sumo-2/3-ylation在快速缺血耐受模型中的变化。预处理对有害缺血后sumo-2/3-基化的影响被蛋白质合成抑制剂放线菌酮（1.0 µM）阻断，放线菌酮是一种已知的延迟缺血耐受抑制剂。此外，我们观察到使用低温（4°C 30 min）作为预处理刺激以诱导延迟缺血耐受的sumo-2/3-ylation减少。进一步的研究表明，sumo-2/3-基化发生在缺血损伤期间，并且预处理不改变sumo E1-和E2-连接酶（UBA 2和Ubc 9）或sumo特异性异肽酶（SenP 1 -3）的表达。虽然sumo-2/3-ylation在细胞应激条件下增强，但尚不清楚这是否是有害的缺血诱导的细胞损伤的原因或结果。
Several recent studies suggest that sumo-2/3 modification of proteins occurs following harmful ischemia, however, sumo-2/3-ylation may also be associated with hibernation-mediated neuroprotection. Here we investigate the sumoylation of proteins following ischemia and ischemic tolerance using our established in vitro model of ischemia (oxygen and glucose deprivation; OGD). Following harmful ischemia (120 min OGD), we observed a significant increase in the sumo-2/3-ylation of high molecular weight proteins (>85 kDa), but not sumo-1-ylation of proteins. Sumo-2/3-ylation following 120 min OGD was reduced when cultures were preconditioned with non-harmful 30 min OGD 24 hours earlier (delayed ischemic tolerance). However, we observed no change in sumo-2/3-ylation in a model of rapid ischemic tolerance. The effects of preconditioning on sumo-2/3-ylation following harmful ischemia was blocked by the protein synthesis inhibitor cycloheximide (1.0 µM), a known inhibitor of delayed ischemic tolerance. In addition, we observed a reduction in sumo-2/3-ylation using hypothermia (4°C 30 min) as the preconditioning stimuli to induce delayed ischemic tolerance. Further studies show sumo-2/3-ylation occurs during the ischemic insult and that preconditioning does not change expression of the sumo E1- and E2-ligases (UBA2 and Ubc9) or the sumo specific isopeptidases (SenP1–3). While sumo-2/3-ylation is enhanced under conditions of cell stress, it is not yet clear whether this is a cause or consequence of harmful ischemia-induced cell damage.
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影响因子：
4.8
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