scholarly journals Phosphorylation-dependent mitochondrial translocation of MAP4 is an early step in hypoxia-induced apoptosis in cardiomyocytes

2014 ◽  
Vol 5 (9) ◽  
pp. e1424-e1424 ◽  
Author(s):  
J Hu ◽  
Z Chu ◽  
J Han ◽  
Q Zhang ◽  
D Zhang ◽  
...  
Keyword(s):  
Early Step ◽  
Mitochondrial Translocation ◽  
Induced Apoptosis

scholarly journals Cyclovirobuxine D Induces Apoptosis and Mitochondrial Damage in Glioblastoma Cells Through ROS-Mediated Mitochondrial Translocation of Cofilin

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Zhang ◽  
Ruoqiu Fu ◽  
Dongyu Duan ◽  
Ziwei Li ◽  
Bin Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Oxidant Stress ◽  
Mitochondrial Damage ◽  
Dependent Manner ◽  
Mitochondrial Translocation ◽  
Mitochondrial Superoxide ◽  
Human Astrocytes ◽  
Anti Cancer ◽  
Normal Human ◽  
Induced Apoptosis

BackgroundCyclovirobuxine D (CVBD), a steroidal alkaloid, has multiple pharmacological activities, including anti-cancer activity. However, the anti-cancer effect of CVBD on glioblastoma (GBM) has seldom been investigated. This study explores the activity of CVBD in inducing apoptosis of GBM cells, and examines the related mechanism in depth.MethodsGBM cell lines (T98G, U251) and normal human astrocytes (HA) were treated with CVBD. Cell viability was examined by CCK-8 assay, and cell proliferation was evaluated by cell colony formation counts. Apoptosis and mitochondrial superoxide were measured by flow cytometry. All protein expression levels were determined by Western blotting. JC-1 and CM-H2DCFDA probes were used to evaluate the mitochondrial membrane potential (MMP) change and intracellular ROS generation, respectively. The cell ultrastructure was observed by transmission electron microscope (TEM). Colocalization of cofilin and mitochondria were determined by immunofluorescence assay.ResultsCVBD showed a greater anti-proliferation effect on the GBM cell lines, T98G and U251, than normal human astrocytes in dose- and time-dependent manners. CVBD induced apoptosis and mitochondrial damage in GBM cells. We found that CVBD led to mitochondrial translocation of cofilin. Knockdown of cofilin attenuated CVBD-induced apoptosis and mitochondrial damage. Additionally, the generation of ROS and mitochondrial superoxide was also induced by CVBD in a dose-dependent manner. N-acetyl-L-cysteine (NAC) and mitoquinone (MitoQ) pre-treatment reverted CVBD-induced apoptosis and mitochondrial damage. MitoQ pretreatment was able to block the mitochondrial translocation of cofilin caused by CVBD.ConclusionsOur data revealed that CVBD induced apoptosis and mitochondrial damage in GBM cells. The underlying mechanism is related to mitochondrial translocation of cofilin caused by mitochondrial oxidant stress.

scholarly journals BimS-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins

2007 ◽  
Vol 177 (4) ◽  
pp. 625-636 ◽  
Author(s):  
Arnim Weber ◽  
Stefan A. Paschen ◽  
Klaus Heger ◽  
Florian Wilfling ◽  
Tobias Frankenberg ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Membrane Insertion ◽  
Apoptosis Induction ◽  
Mitochondrial Targeting ◽  
Mitochondrial Localization ◽  
Mitochondrial Translocation ◽  
Killing Activity ◽  
Regulated Expression ◽  
Direct Binding ◽  
Induced Apoptosis

Release of apoptogenic proteins such as cytochrome c from mitochondria is regulated by pro- and anti-apoptotic Bcl-2 family proteins, with pro-apoptotic BH3-only proteins activating Bax and Bak. Current models assume that apoptosis induction occurs via the binding and inactivation of anti-apoptotic Bcl-2 proteins by BH3-only proteins or by direct binding to Bax. Here, we analyze apoptosis induction by the BH3-only protein BimS. Regulated expression of BimS in epithelial cells was followed by its rapid mitochondrial translocation and mitochondrial membrane insertion in the absence of detectable binding to anti-apoptotic Bcl-2 proteins. This caused mitochondrial recruitment and activation of Bax and apoptosis. Mutational analysis of BimS showed that mitochondrial targeting, but not binding to Bcl-2 or Mcl-1, was required for apoptosis induction. In yeast, BimS enhanced the killing activity of Bax in the absence of anti-apoptotic Bcl-2 proteins. Thus, cell death induction by a BH3-only protein can occur through a process that is independent of anti-apoptotic Bcl-2 proteins but requires mitochondrial targeting.

scholarly journals Stretching magnitude–dependent inactivation of AKT by ROS led to enhanced p53 mitochondrial translocation and myoblast apoptosis

2019 ◽  
Vol 30 (10) ◽  
pp. 1182-1197 ◽  
Author(s):  
Jing Song ◽  
Yaqi Wang ◽  
Xiao Yuan ◽  
Qiuxia Ji ◽  
Cunhui Fan ◽  
...  
Keyword(s):  
P53 Protein ◽  
Akt Pathway ◽  
Ros Generation ◽  
C2c12 Myoblast ◽  
Wild Type ◽  
Nuclear Targeting ◽  
Mitochondrial Translocation ◽  
Dependent Inactivation ◽  
Mitochondrial Trafficking ◽  
Induced Apoptosis

Previously, we had shown that high magnitude stretch (HMS), rather than low magnitude stretch (LMS), induced significant apoptosis of skeletal muscle C2C12 myoblasts. However, the molecular mechanism remains obscure. In this study, we found that p53 protein accumulated in the nucleus of LMS-loaded cells, whereas it translocated into mitochondria of HMS-loaded cells. Knocking down endogenous p53 by shRNA abrogated HMS-induced apoptosis. Furthermore, we demonstrated that overaccumulation of reactive oxygen species (ROS) during HMS-inactivated AKT that was activated in LMS-treated cells, which accounted for the distinct p53 subcellular localizations under HMS and LMS. Blocking ROS generation by N-acetylcysteine (NAC) or overexpressing constitutively active AKT vector (CA-AKT) inhibited HMS-incurred p53 mitochondrial translocation and promoted its nuclear targeting. Moreover, both NAC and CA-AKT significantly attenuated HMS-induced C2C12 apoptosis. Finally, we found that Ser389 phosphorylation of p53 was a downstream event of ROS-inactivated AKT pathway, which was critical to p53 mitochondrial trafficking during HMS stimuli. Transfecting p53-shRNA C2C12s with the mutant p53 (S389A) that was unable to target p53 to mitochondria underwent significantly lower apoptosis than transfection with wild-type p53. Altogether, our study uncovered that mitochondrial localization of p53, resulting from p53 Ser389 phosphorylation through ROS-inactivated AKT pathway, prompted C2C12 myoblast apoptosis during HMS stimulation.

scholarly journals Conformational change and mitochondrial translocation of Bax accompany proteasome inhibitor-induced apoptosis of chronic lymphocytic leukemic cells

Oncogene ◽  
2003 ◽  
Vol 22 (17) ◽  
pp. 2643-2654 ◽  
Author(s):  
Grant Dewson ◽  
Roger T Snowden ◽  
Jason B Almond ◽  
Martin J S Dyer ◽  
Gerald M Cohen
Keyword(s):  
Conformational Change ◽  
Proteasome Inhibitor ◽  
Leukemic Cells ◽  
Mitochondrial Translocation ◽  
Induced Apoptosis
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