The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo.
The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo.
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DOI：
10.1002/ana.21548
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发表时间：
2008-12
影响因子：
11.2
通讯作者：
Tanzi, Rudolph E.
中科院分区：
文献类型：
--
作者：
Xie, Zhongcong;Culley, Deborah J.;Dong, Yuanlin;Zhang, Guohua;Zhang, Bin;Moir, Robert D.;Frosch, Matthew P.;Crosby, Gregory;Tanzi, Rudolph E.
据估计，全世界每年有2亿患者接受手术。据报道，麻醉和手术有助于阿尔茨海默病（AD）的出现。此前已报道常用的吸入麻醉剂异氟烷可诱导细胞凋亡，并增加培养细胞中AD相关淀粉样β蛋白（Aβ）的水平和聚集。然而，体内相关性尚未得到解决。因此，我们采用Western blot、免疫组织化学和RT-PCR确定异氟烷对未处理小鼠中caspase活化、BACE和Aβ水平的影响。在这里，我们首次表明，临床相关的异氟烷麻醉（1.4%异氟烷持续两小时）会导致小鼠大脑麻醉后六小时的半胱天冬酶激活和β位点APP切割酶（BACE）水平适度增加。异氟烷麻醉诱导caspase活化，增加BACE和Aβ水平，直至麻醉后24小时。异氟烷可能通过减少BACE降解而升高BACE水平。此外，Aβ聚集抑制剂氯碘羟喹能够减弱异氟烷诱导的体内caspase-3活化。鉴于短暂的脑损伤可能导致长期脑损伤，这些结果表明异氟烷可能促进AD神经发病机制，因此，对人体使用异氟烷具有影响，有待人体研究证实。
An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer’s disease (AD). The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis and to increase levels and aggregation of AD-associated amyloid β-protein (Aβ) in cultured cells. However, the in vivo relevance has not been addressed. We therefore set out to determine effects of isoflurane on caspase activation, levels of BACE and Aβ in naïve mice, employing Western blot, immunohistochemistry and RT-PCR. Here we show for the first time that a clinically relevant isoflurane anesthesia (1.4% isoflurane for two hours) leads to caspase activation and modest increases in levels of the β-site APP-cleaving enzyme (BACE) six hours after anesthesia in mouse brain. Isoflurane anesthesia induces caspase activation, increases levels of BACE and Aβ up to 24 hours after anesthesia. Isoflurane may increase BACE levels by reducing BACE degradation. Moreover, the Aβ aggregation inhibitor, clioquinol, was able to attenuate isoflurane-induced caspase-3 activation in vivo. Given that transient insults to brain may lead to long term brain damage, these findings suggest that isoflurane may promote AD neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending on human study confirmation.
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影响因子：
3.3
作者：
Grace, EA;Rabiner, CA;Busciglio, J
通讯作者：
Busciglio, J
影响因子：
2.1
作者：
LeBlanc, Andrea C.
通讯作者：
LeBlanc, Andrea C.
影响因子：
2.9
作者：
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通讯作者：
Trommer, BL
影响因子：
8.8
作者：
Xie, ZC;Dong, YL;Tanzi, RE
通讯作者：
Tanzi, RE
影响因子：
--
作者：
Thornberry, NA
通讯作者：
Thornberry, NA