Ghrelin ameliorates A549 cell apoptosis caused by paraquat via p38-MAPK regulated mitochondrial apoptotic pathway

Toxicology ◽  
2019 ◽  
Vol 426 ◽  
pp. 152267 ◽  
Author(s):  
Shuqing Cui ◽  
Qing Nian ◽  
Gang Chen ◽  
Xingyong Wang ◽  
Jinying Zhang ◽  
...  
Keyword(s):  
P38 Mapk ◽  
A549 Cell ◽  
Cell Apoptosis ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway

scholarly journals Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax

2016 ◽  
Vol 90 (21) ◽  
pp. 9862-9877 ◽  
Author(s):  
Haolong Cong ◽  
Ning Du ◽  
Yang Yang ◽  
Lei Song ◽  
Wenliang Zhang ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Enterovirus 71 ◽  
Terminal Region ◽  
Ev71 Infection ◽  
Apoptotic Pathway ◽  
Hydrophobic Region ◽  
Mitochondrial Apoptotic Pathway ◽  
Proapoptotic Protein ◽  
2B Protein ◽  
Induced Apoptosis

ABSTRACTTo survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochromec(Cytc) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XLabrogates 2B-induced release of Cytcand caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax.IMPORTANCEEV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. This study provides evidence that EV71 induces cell apoptosis by modulating Bax activation and reveals important clues regarding the mechanism of Cytcrelease and mitochondrial permeabilization during EV71 infection.

scholarly journals Paris Polyphylla Monomer PP-26 Induces Mitochondrial Pathway-Mediated Cell Apoptosis by Inhibiting the PI3K/Akt Pathway in Human Gastric Cancer Cells

2021 ◽  
Author(s):  
Jiajin Chen ◽  
Junzhen Zhou ◽  
Jun Xu ◽  
Na Zhao ◽  
Qiang Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Cell Apoptosis ◽  
Mitochondrial Membrane ◽  
Akt Pathway ◽  
Caspase Inhibitor ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Paris Polyphylla

Abstract Background: Paris polyphylla is a traditional Chinese medicinal herb that has been used as a haemostatic, antimicrobial and anticancer agent. Gastric cancer (GC) is a global health problem, with more than 1 million people newly diagnosed with gastric cancer worldwide each year.Methods: The MTT and colony formation assay were used to test the anti-proliferative effects of PP-26 on MGC-803 and BGC-823 cells. Flow cytometry assays, Hoechst 33258 staining assay and Caspase inhibitor Z-VAD-FMK were used to test apoptosis. JC-1 staining used to measure changes in mitochondrial membrane potential and western blot analysis were used to test apoptotic and PI3K/Akt pathway related proteins.Results: PP-26 had a dose-dependent inhibitory effect on the proliferation of MGC-803 and BGC-823 cells, but had no obvious anti-proliferative effect on normal liver LO2 cells and normal embryonic kidney HEK-293 cells. Additionally, PP-26 induced typical apoptotic morphological changes, such as nuclear pyknosis, nuclear cracking and apoptotic bodies. Moreover, PP-26 induced a decrease in mitochondrial membrane potential. And PP-26 modulated the expression of Bcl-xL, Mcl-1, Bax, caspase-9/-3 and PARP proteins and induced cell apoptosis through the mitochondrial apoptotic pathway. Next, using an irreversible general caspase inhibitor (Z-VAD-FMK), we confirmed the activation of the mitochondrial apoptotic pathway induced by PP-26. Furthermore, PP-26 inhibited the phosphorylation of Akt and GSK-3β. The inhibition of Akt protein activated the mitochondrial apoptotic pathway.Conclusion: Collectively, these results indicated that PP-26 inhibited the proliferation of MGC-803 and BGC-823 cells by inhibiting the Akt signalling pathway and activating the mitochondrial apoptotic pathway.

scholarly journals Zika virus infection induced apoptosis by modulating the recruitment and activation of pro-apoptotic protein Bax

2021 ◽  
Author(s):  
Xiaodong Han ◽  
Jiuqiang Wang ◽  
Yang Yang ◽  
Shuxiang Qu ◽  
Fang Wan ◽  
...  
Keyword(s):  
Zika Virus ◽  
Cell Apoptosis ◽  
Zikv Infection ◽  
Apoptotic Pathway ◽  
Subsequent Formation ◽  
Mitochondrial Apoptotic Pathway ◽  
Detailed Mechanism ◽  
Apoptotic Protein ◽  
Cyt C ◽  
Induced Apoptosis

Zika virus (ZIKV) infection is associated with microcephaly in newborns and serious neurological complications in adults. Apoptosis of neural progenitor cells induced by ZIKV infection is believed to be a main reason for ZIKV infection-related microcephaly. However, the detailed mechanism of ZIKV infection-induced apoptosis remains to be elucidated. In this report, ZIKV infection induced the conformational activation of the pro-apoptotic protein Bax, with subsequent formation of oligomers of Bax in the mitochondria. Cell apoptosis was reduced significantly in SY5Y cells subjected to Bax knockdown. Additionally, while decreasing Bax expression inhibited the release of Cyt c from the mitochondria and reduced the rate of loss of mitochondrial membrane potential induced by ZIKV infection, silencing Bak, caspase-8, and/or caspase-10 expression did not. Mitochondria isolated from the untreated ZIKV-infected cells displayed Bax-binding ability and the subsequent release of Cyt c. This study also indicated that the NS4B protein of ZIKV recruited Bax to the mitochondria and induced Bax conformational activation. The overexpressed NS4B was localized to the mitochondria and induced cell apoptosis by activating the pro-apoptotic protein Bax. All the above results indicated that ZIKV infection directly impacted the mitochondrial apoptotic pathway by modulating the recruitment and activation of Bax. Importance: Since the large outbreaks that occurred in the Pacific Islands and Latin America in 2013, Zika virus has been confirmed a neuroteratogenic pathogen and causative agent of microcephaly and other developmental anomalies of the central nervous system in children born to infected mothers. As the widespread apoptosis throughout the whole brain, studies in animal models have reinforced the link between microcephaly caused by ZIKV infection and NPC apoptosis. Currently, the detailed mechanism of ZIKV infection-induced apoptosis still remains to be elucidated. Here, we firstly demonstrate that ZIKV infection activated the classic signs of mitochondrial apoptotic pathway by modulating the recruitment and activation of Bax. ZIKV NS4B represents a novel viral apoptotic protein that can modulate the recruitment and activation of Bax and trigger the apoptotic program. This is a new insight into understanding the interplay between apoptosis and ZIKV infection.

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