Polyglutamine expansion disturbs the endoplasmic reticulum formation, leading to caspase-7 activation through Bax.
Polyglutamine expansion disturbs the endoplasmic reticulum formation, leading to caspase-7 activation through Bax.
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聚谷氨酰胺扩张扰乱内质网形成，导致通过 Bax 激活 caspase-7。
DOI：
10.1016/j.bbrc.2013.12.114
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Nakagawa T
中科院分区：
文献类型：
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作者：
Ueda M;Li S;Itoh M;Hayakawa-Yano Y;Wang MX;Hayakawa M;Hasebe-Matsubara R;Ohta K;Ohta E;Mizuno A;Matsumoto M;Chen H;Hida Y;Nakagawa T
内质网 (ER) 在 ER 应激反应等细胞功能中发挥着关键作用。然而，内质网膜对半胱天冬酶激活的影响仍不清楚。这项研究表明，ER 处增强的聚谷氨酰胺寡聚物诱导 Bax 插入 ER 膜，从而激活 caspase-7。与内质网在多聚谷氨酰胺扩张诱导的细胞死亡中的作用一致，我们发现亨廷顿病小鼠模型的大脑中内质网膜被破坏和扩张。我们可以得出结论，聚谷氨酰胺扩增可能通过破坏内质网膜来驱动 caspase-7 激活。
The endoplasmic reticulum (ER) plays a pivotal role in cellular functions such as the ER stress response. However, the effect of the ER membrane on caspase activation remains unclear. This study reveals that polyglutamine oligomers augmented at ER induce insertion of Bax into the ER membrane, thereby activating caspase-7. In line with the role of ER in cell death induced by polyglutamine expansion, the ER membrane was found to be disrupted and dilated in the brain of a murine model of Huntington’s disease. We can conclude that polyglutamine expansion may drive caspase-7 activation by disrupting the ER membrane.