Involvement of fish signal transducer and activator of transcription 3 (STAT3) in nodavirus infection induced cell death

2015 ◽  
Vol 43 (1) ◽  
pp. 241-248 ◽  
Author(s):  
Youhua Huang ◽  
Xiaohong Huang ◽  
Ying Yang ◽  
Wei Wang ◽  
Yepin Yu ◽  
...  
Keyword(s):  
Cell Death ◽  
Signal Transducer ◽  
Transcription 3 ◽  
Fish Signal

scholarly journals Down-regulation of MicroRNA-21 Is Involved in the Propofol-induced Neurotoxicity Observed in Human Stem Cell–derived Neurons

2014 ◽  
Vol 121 (4) ◽  
pp. 786-800 ◽  
Author(s):  
Danielle M. Twaroski ◽  
Yasheng Yan ◽  
Jessica M. Olson ◽  
Zeljko J. Bosnjak ◽  
Xiaowen Bai
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Signal Transducer ◽  
Deoxyuridine Triphosphate ◽  
Transcription 3

Abstract Background: Recent studies in various animal models have suggested that anesthetics such as propofol, when administered early in life, can lead to neurotoxicity. These studies have raised significant safety concerns regarding the use of anesthetics in the pediatric population and highlight the need for a better model to study anesthetic-induced neurotoxicity in humans. Human embryonic stem cells are capable of differentiating into any cell type and represent a promising model to study mechanisms governing anesthetic-induced neurotoxicity. Methods: Cell death in human embryonic stem cell–derived neurons was assessed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling staining, and microRNA expression was assessed using quantitative reverse transcription polymerase chain reaction. miR-21 was overexpressed and knocked down using an miR-21 mimic and antagomir, respectively. Sprouty 2 was knocked down using a small interfering RNA, and the expression of the miR-21 targets of interest was assessed by Western blot. Results: Propofol dose and exposure time dependently induced significant cell death (n = 3) in the neurons and down-regulated several microRNAs, including miR-21. Overexpression of miR-21 and knockdown of Sprouty 2 attenuated the increase in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling–positive cells following propofol exposure. In addition, miR-21 knockdown increased the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling–positive cells by 30% (n = 5). Finally, activated signal transducer and activator of transcription 3 and protein kinase B (Akt) were down-regulated, and Sprouty 2 was up-regulated following propofol exposure (n = 3). Conclusions: These data suggest that (1) human embryonic stem cell–derived neurons represent a promising in vitro human model for studying anesthetic-induced neurotoxicity, (2) propofol induces cell death in human embryonic stem cell–derived neurons, and (3) the propofol-induced cell death may occur via a signal transducer and activator of transcription 3/miR-21/Sprouty 2–dependent mechanism.

scholarly journals STAT3 Enhances Sensitivity of Glioblastoma to Drug-Induced Autophagy-Dependent Cell Death

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 339
Author(s):  
Janina Remy ◽  
Benedikt Linder ◽  
Ulrike Weirauch ◽  
Bryan W. Day ◽  
Brett W. Stringer ◽  
...  
Keyword(s):  
Cell Death ◽  
Major Influence ◽  
Signal Transducer ◽  
Drug Induced ◽  
Lysosomal Membrane Permeabilization ◽  
Dismal Prognosis ◽  
Dependent Cell ◽  
Autophagy Pathway ◽  
One Year ◽  
Transcription 3

Glioblastoma (GBM) is a devastating disease and the most common primary brain malignancy of adults with a median survival barely exceeding one year. Recent findings suggest that the antipsychotic drug pimozide triggers an autophagy-dependent, lysosomal type of cell death in GBM cells with possible implications for GBM therapy. One oncoprotein that is often overactivated in these tumors and associated with a particularly dismal prognosis is Signal Transducer and Activator of Transcription 3 (STAT3). Here, we used isogenic human and murine GBM knockout cell lines, advanced fluorescence microscopy, transcriptomic analysis and FACS-based assessment of cell viability to show that STAT3 has an underappreciated, context-dependent role in drug-induced cell death. Specifically, we demonstrate that depletion of STAT3 significantly enhances cell survival after treatment with Pimozide, suggesting that STAT3 confers a particular vulnerability to GBM. Furthermore, we show that active STAT3 has no major influence on the early steps of the autophagy pathway, but exacerbates drug-induced lysosomal membrane permeabilization (LMP) and release of cathepsins into the cytosol. Collectively, our findings support the concept of exploiting the pro-death functions of autophagy and LMP for GBM therapy and to further determine whether STAT3 can be employed as a treatment predictor for highly apoptosis-resistant, but autophagy-proficient cancers.

Involvement of fish signal transducer and activator of transcription 3 (STAT3) in SGIV replication and virus induced paraptosis

2014 ◽  
Vol 41 (2) ◽  
pp. 308-316 ◽  
Author(s):  
Xiaohong Huang ◽  
Youhua Huang ◽  
Ying Yang ◽  
Shina Wei ◽  
Qiwei Qin
Keyword(s):  
Signal Transducer ◽  
Transcription 3 ◽  
Fish Signal

scholarly journals The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3

2003 ◽  
Vol 100 (16) ◽  
pp. 9342-9347 ◽  
Author(s):  
J. Zhang ◽  
J. Yang ◽  
S. K. Roy ◽  
S. Tininini ◽  
J. Hu ◽  
...  
Keyword(s):  
Cell Death ◽  
Signal Transducer ◽  
Transcription 3

scholarly journals Isolinderalactone Induces Cell Death via Mitochondrial Superoxide- and STAT3-Mediated Pathways in Human Ovarian Cancer Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7530
Author(s):  
Shakya Rajina ◽  
Woo Jean Kim ◽  
Jung-Hyun Shim ◽  
Kyung-Soo Chun ◽  
Sang Hoon Joo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cells ◽  
Signal Transducer ◽  
Antitumor Activities ◽  
Mitochondrial Superoxide ◽  
Dependent Cell ◽  
Transcription 3 ◽  
Cell Proportion

The mortality rate of ovarian cancer (OC) worldwide increases with age. OC is an often fatal cancer with a curative rate of only 20–30%, as symptoms often appear after disease progression. Studies have reported that isolinderalactone (ILL), a furanosesquiterpene derivative extracted from the dried root of Lindera aggregata, can inhibit several cancer cell lines’ growth. However, the molecular mechanisms underlying ILL activities in human OC cells remain unexplored. This study investigated the antitumor activities of ILL in human OC cells by inducing mitochondrial superoxide (mtSO) and JAK-signal transducer and activator of transcription 3 (STAT3)-dependent cell death. ILL caused cell death in SKOV-3 and OVCAR-3 cells and increased the cell proportion in the subG1 phase. Additionally, ILL significantly induced mtSO production and reduced ROS production. Moreover, ILL downregulated mitochondrial membrane potential and the expression levels of anti-apoptotic Bcl-2 family proteins and superoxide dismutase (SOD)2. Results showed that ILL decreased phosphorylation of serine 727 and tyrosine 705 of STAT3 and expression of survivin, a STAT3-regulated gene. Furthermore, ILL-induced cell death was reversed by pretreatment of Mito-TEMPO, a mitochondria-specific antioxidant. These results suggest that ILL induces cell death by upregulation of mtSO, downregulation of mitochondrial SOD2, and inactivation of the STAT3-mediated pathway.

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