Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection.
Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection.
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DOI：
10.1097/aln.0b013e3181d3d624
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发表时间：
2010-05
期刊：
影响因子：
8.8
通讯作者：
Patel HH
中科院分区：
文献类型：
--
作者：
Tsutsumi YM;Kawaraguchi Y;Horikawa YT;Niesman IR;Kidd MW;Chin-Lee B;Head BP;Patel PM;Roth DM;Patel HH
小凹是质膜的小烧瓶状内陷。小窝蛋白是在小窝中发现的结构蛋白，具有支架特性，可以组织信号传导。我们测试了以下假设：挥发性麻醉药引起的心脏保护延迟是小凹/小凹蛋白依赖性的。在野生型、caveolin-1 敲除小鼠和 Caveolin-3 敲除小鼠中测试了延迟麻醉预处理的体内缺血再灌注损伤小鼠模型。将小鼠暴露于氧气或异氟烷中 30 分钟，并允许其恢复 24 小时。 24小时恢复后，小鼠接受30分钟的冠状动脉闭塞，然后再灌注2小时，此时确定梗塞面积。还在切除的心脏中进行了生化测定。在野生型小鼠（24.0 ± 8.8% vs. 45.1 ± 10.1%）和 Caveolin-1 敲除小鼠（27.2 ± 12.5%）中，异氟醚降低了梗死面积占危险区域的百分比。 Caveolin-3 基因敲除小鼠未表现出延迟麻醉预处理 (41.5 ± 5.0%)。在野生型和 Caveolin-1 敲除小鼠中观察到了显微镜下明显的小凹，但在 Caveolin-3 敲除小鼠中未观察到。延迟麻醉预处理增加了不连续蔗糖梯度浮力级分中 Caveolin-3 蛋白的含量，但没有增加 Caveolin-1 蛋白的含量。此外，麻醉预处理后，在野生型和 Caveolin-1 敲除小鼠中观察到浮力组分中的葡萄糖转运蛋白 4 增加，并且观察到 Caveolin-3/葡萄糖转运蛋白 4 共定位。这些结果表明，延迟麻醉预处理涉及小窝蛋白 3 和葡萄糖转运蛋白 4 易位至小窝，导致心肌延迟保护。
Caveolae are small, flask-like invaginations of the plasma membrane. Caveolins are structural proteins found in caveolae that have scaffolding properties to allow organization of signaling. We tested the hypothesis that delayed cardiac protection induced by volatile anesthetics is caveolae/caveolin-dependent. An in vivo mouse model of ischemia-reperfusion injury with delayed anesthetic preconditioning was tested in wild-type, caveolin-1 knockout, and caveolin-3 knockout mice. Mice were exposed to 30 min oxygen or isoflurane and allowed to recover for 24 h. After 24 h recovery, mice underwent 30 min coronary artery occlusion, followed by 2 h of reperfusion at which time infarct size was determined. Biochemical assays were also performed in excised hearts. Infarct size as a percent of the area at risk was reduced by isoflurane in wild-type (24.0 ± 8.8% vs. 45.1 ± 10.1%) and caveolin-1 knockout mice (27.2 ± 12.5%). Caveolin-3 knockout mice did not show delayed anesthetic preconditioning (41.5 ± 5.0%). Microscopically distinct caveolae were observed in wild-type and caveolin-1 knockout mice but not caveolin-3 knockout mice. Delayed anesthetic preconditioning increased the amount of caveolin-3 protein but not caveolin-1 protein in discontinuous sucrose gradient buoyant fractions. Additionally, glucose transporter-4 was increased in buoyant fractions and caveolin-3/glucose transporter-4 colocalization was observed in wild-type and caveolin-1 knockout mice after anesthetic preconditioning. These results demonstrate that delayed anesthetic preconditioning involves translocation of caveolin-3 and glucose transporter-4 to caveolae resulting in delayed protection in the myocardium.