Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress
Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress
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Caspase-12 参与拉伸诱导的细胞凋亡介导的内质网应激
DOI：
10.1007/s10495-016-1217-6
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发表时间：
2016-04-01
期刊：
影响因子：
7.2
通讯作者：
Yuan, Xiao
中科院分区：
文献类型：
--
作者：
Zhang, Qiang;Liu, Jianing;Yuan, Xiao
众所周知，下颌骨的生长是由各种功能器具引起的，被认为是神经肌肉和骨骼适应的结果。越来越多的证据表明，细胞凋亡在骨骼肌功能的适应中起着重要的作用。然而，拉伸诱导细胞凋亡的潜在机制仍然不完全清楚。内质网应激（Endoplasmic reticulum stress， ERS）是一种新发现的细胞凋亡信号通路。本研究旨在确定caspase-12是否参与拉伸诱导的细胞凋亡介导的成肌细胞内质网应激及其潜在机制。采用Hochest染色、DAPI染色、膜联蛋白V结合及PI染色观察细胞凋亡情况。逆转录聚合酶链反应（RT-PCR）和Western blot检测ER伴侣蛋白GRP78、CHOP、caspase-12。此外，我们还利用caspase-12抑制剂来评估caspase-12通路的机制。在周期性拉伸作用下，观察到成肌细胞凋亡呈时间依赖性。我们发现，在循环拉伸的成肌细胞中，GRP78 mRNA和蛋白显著升高，CHOP和caspase-12被激活。Caspase-12抑制可减少拉伸诱导的细胞凋亡，Caspase-12激活caspase-3诱导细胞凋亡。我们得出结论，caspase-12通过激活caspase-3在内质网应激相关的拉伸诱导细胞凋亡中发挥重要作用。
It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3.