Mitochondrial translocation of cofilin is required for allyl isothiocyanate-mediated cell death via ROCK1/PTEN/PI3K signaling pathway

Cell Communication and Signaling

Research

Ting Zhou¹  Chang-yu Shan¹  Xiao-ye Hu¹  Qi Cheng¹  Jing Zhou¹  Lei Liu¹  Guo-bing Li¹  Ning Gao¹  E-hu Liu²  Ping Li² 

[1] Department of Pharmacognosy, College of Pharmacy, 3rd Military Medical University, 400038, Chongqing, China;State Key Laboratory of Natural Medicines (China Pharmaceutical University), 210009, Nanjing, China;

关键词: Allyl isothiocyanate;    Apoptosis;    Cofilin;    ROCK1;    PI3K;    Leukemia;   

DOI  :  10.1186/1478-811X-11-50

 received in 2013-06-01, accepted in 2013-07-17,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCofilin is a member of the actin depolymerizing factor (ADF)/cofilin family, which regulates actin dynamics. Increasing evidence suggests that mitochondrial translocation of cofilin appears necessary for the regulation of apoptosis.ResultsWe report that allyl isothiocyanate (AITC) potently induces mitochondria injury and apoptosis. These events were accompanied by a loss of polymerized filamentous actin (F-actin) and increase in unpolymerized globular actin (G-actin). AITC also induces dephosphorylation of cofilin through activation of PP1 and PP2A. Only dephosphorylated cofilin binds to G-actin and translocates to mitochondria during AITC-mediated apoptosis. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K signaling pathway plays a critical role in AITC-mediated dephosphorylation and mitochondrial translocation of cofilin and apoptosis. Our in vivo study also showed that AITC-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with dephosphorylation of cofilin.ConclusionsThese findings support a model in which induction of apoptosis by AITC stems primarily from activation of ROCK1 and PTEN, and inactivation of PI3K, leading in turn to activation of PP1 and PP2A, resulting in dephosphorylation of cofilin, which binds to G-actin and translocates to mitochondria, culminating in the dysfunction of mitochondria, release of cytochrome c and apoptosis.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.