Protection From Apoptotic Cell Death During Cold Storage Followed by Rewarming in 13-Lined Ground Squirrel Tubular Cells: The Role of Prosurvival Factors X-Linked Inhibitor of Apoptosis and PhosphoAkt.
Protection From Apoptotic Cell Death During Cold Storage Followed by Rewarming in 13-Lined Ground Squirrel Tubular Cells: The Role of Prosurvival Factors X-Linked Inhibitor of Apoptosis and PhosphoAkt.
复制标题
DOI：
10.1097/tp.0000000000000937
复制
发表时间：
2016-03
期刊：
影响因子：
6.2
通讯作者：
Jani A
中科院分区：
文献类型：
--
作者：
Jain S;Keys D;Martin S;Edelstein CL;Jani A
冬眠动物，如13线地松鼠忍受严重的低温在麻痹期间，然后在间歇唤醒（IBA）期间定期复温，促凋亡条件是致命的非冬眠哺乳动物。我们以前已经表明，13线地松鼠肾小管细胞的保护，从凋亡细胞死亡在IBA。为了了解保护机制，我们开发了一种体外模型，长期冷藏，然后复温（CS/REW），这是类似于体内的变化，低温，然后在IBA观察复温。我们假设从冬眠的地松鼠中分离的肾小管上皮细胞（RTECs）在CS/REW期间与非冬眠的小鼠RTECs相比将被保护免受凋亡。将隔离的冬眠地松鼠和小鼠RTEC在4°C下冷藏24小时，然后复温至37°C持续24小时（CS/REW）。地松鼠RTECs有显着较少的细胞凋亡相比，小鼠RTECs时，受到CS/REW。接下来，我们假设保护机制与抗凋亡蛋白XIAP、pAkt和pBAD有关。与小鼠RTEC相比，地松鼠在CS/REW下的pAkt和pBAD表达显著增加。XIAP表达在地松鼠RTECs中维持，但在CS/REW后小鼠RTECs中显著降低。其中Akt 1和XIAP基因表达沉默的地松鼠RTEC失去了它们的保护作用，并且在CS/REW后表现出增加的凋亡和切割的半胱天冬酶-3表达。我们的研究结果表明，在延长CS/REW期间，地松鼠RTECs通过“促生存”因子XIAP和pAkt而免受凋亡。
Hibernators such as the 13-lined ground squirrel endure severe hypothermia during torpor followed by periodic rewarming during interbout arousal (IBA), pro-apoptotic conditions that are lethal to non-hibernating mammals. We have previously shown that 13-lined ground squirrel tubular cells are protected from apoptotic cell death during IBA. To understand the mechanism of protection, we developed an in vitro model of prolonged cold storage followed by rewarming (CS/REW), which is akin to the in vivo changes of hypothermia followed by rewarming observed during IBA. We hypothesized that renal tubular epithelial cells (RTECs) isolated from hibernating ground squirrels would be protected against apoptosis during CS/REW, vs. non-hibernating mouse RTECs. Isolated hibernating ground squirrel and mouse RTECs were subjected to cold storage at 4°C for 24 hours followed by rewarming to 37°C for 24 hours (CS/REW). Ground squirrel RTECs had significantly less apoptosis compared to mouse RTECs when subjected to CS/REW. Next, we hypothesized that the mechanism of protection was related to the anti-apoptotic proteins XIAP, pAkt and pBAD. There was significantly increased pAkt and pBAD expression in ground squirrel vs. mouse RTECs subjected to CS/REW. XIAP expression was maintained in ground squirrel RTECs but was significantly decreased in mouse RTECs following CS/REW. Ground squirrel RTECs in which gene expression of Akt1 and XIAP was silenced lost their protection and demonstrated increased apoptosis & cleaved capase-3 expression following CS/REW. Our findings suggest that ground squirrel RTECs are protected against apoptosis during prolonged CS/REW by the ‘pro-survival’ factors XIAP and pAkt.