Heat stress induced apoptosis is triggered by transcription-independent p53, Ca(2+) dyshomeostasis and the subsequent Bax mitochondrial translocation.
Heat stress induced apoptosis is triggered by transcription-independent p53, Ca(2+) dyshomeostasis and the subsequent Bax mitochondrial translocation.
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DOI：
10.1038/srep11497
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发表时间：
2015-06-24
影响因子：
4.6
通讯作者：
Su L
中科院分区：
文献类型：
--
作者：
Gu ZT;Li L;Wu F;Zhao P;Yang H;Liu YS;Geng Y;Zhao M;Su L
在本研究中，我们证明了Bax线粒体易位在热应激激活的线粒体信号通路的启动中起着至关重要的作用。此外，p53线粒体易位和Ca ~（2+）信号介导的MPTP开放均激活Bax线粒体易位。采用p53线粒体转位抑制剂pifithrin-α和渗透性转换孔（permeability transition pore，MPTP）抑制剂CsA，发现PFT和CsA均能显著抑制热应激诱导的Bax线粒体转位。此外，我们证明了活性氧（ROS）的产生是热应激诱导细胞凋亡的关键介质，抗氧化剂MnTBAP显著降低热应激诱导的p53线粒体易位和Ca 2+信号介导的MPTP开放，以及随后的Bax线粒体易位和caspase级联的激活。两者合计，我们的研究结果表明，热应激诱导细胞凋亡，通过线粒体途径与ROS依赖性线粒体p53易位和Ca 2+动态平衡失调，以及随后的线粒体内Bax易位作为上游事件参与触发细胞暴露于热应激后观察到的凋亡过程。
In this study, We demonstrated that Bax mitochondrial translocation plays a vital role in the initiation of the mitochondrial signaling pathway upon activation by heat stress. In addition, both p53 mitochondrial translocation and Ca2+ signal mediated MPTP opening activate Bax mitochondrial translocation. Employing pifithrin-α (a p53 mitochondrial translocation inhibitor) and CsA (a permeability transition pore (MPTP) inhibitor), we found that heat stress induced Bax mitochondrial translocation was significantly inhibited in cells pretreated with both PFT and CsA. Furthermore, we demonstrated that generation of reactive oxygen species (ROS) is a critical mediator in heat stress induced apoptosis and that the antioxidant MnTBAP significantly decreased heat stress induced p53 mitochondrial translocation and Ca2+ signal mediated MPTP opening, as well as the subsequent Bax mitochondrial translocation and activation of the caspase cascade. Taken together, our results indicate that heat stress induces apoptosis through the mitochondrial pathway with ROS dependent mitochondrial p53 translocation and Ca2+ dyshomeostasis, and the ensuing intro Bax mitochondrial translocation as the upstream events involved in triggering the apoptotic process observed upon cellular exposure to heat stress.
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影响因子：
3.1
作者：
Brinton, Mark R.;Tagge, Chad A.;Stewart, Russell J.;Cheung, Alfred K.;Shiu, Yan-Ting E.;Christensen, Douglas A.
通讯作者：
Christensen, Douglas A.
影响因子：
4.6
作者：
Banerjee, Kaushik;Ganguly, Avishek;Choudhuri, Soumitra Kumar
通讯作者：
Choudhuri, Soumitra Kumar
影响因子：
4
作者：
Kim, Kwang-Youn;Cho, Hyo-Jin;Ahn, Soon-Cheol
通讯作者：
Ahn, Soon-Cheol
影响因子：
4.5
作者：
Horimoto, Kanna;Nishimura, Yumiko;Oyama, Yasuo
通讯作者：
Oyama, Yasuo
DOI：
10.1074/jbc.m109.025353
发表时间：
2009-07-31
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Baumgartner HK;Gerasimenko JV;Thorne C;Ferdek P;Pozzan T;Tepikin AV;Petersen OH;Sutton R;Watson AJ;Gerasimenko OV
通讯作者：
Gerasimenko OV