scholarly journals Tianma Gouteng Decoction regulates oxidative stress and inflammation in AngII-induced hypertensive mice via transcription factor EB to exert anti-hypertension effect

2022 ◽  
Vol 145 ◽  
pp. 112383
Author(s):  
Linhua Deng ◽  
Wei Liu ◽  
Qiang Xu ◽  
Rui Guo ◽  
Dapeng Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcription Factor Eb

scholarly journals Transcription factor EB (TFEB)-mediated autophagy protects bovine mammary epithelial cells against H2O2-induced oxidative damage in vitro

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xudong Sun ◽  
Renxu Chang ◽  
Yan Tang ◽  
Shengbin Luo ◽  
Chunhui Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Oxidative Damage ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Protein Abundance ◽  
Bovine Mammary Epithelial Cells ◽  
Ros Accumulation ◽  
Transcription Factor Eb

Abstract Background Bovine mammary epithelial cells after calving undergo serious metabolic challenges and oxidative stress both of which could compromise autophagy. Transcription factor EB (TFEB)-mediated autophagy is an important cytoprotective mechanism against oxidative stress. However, effects of TFEB-mediated autophagy on the oxidative stress of bovine mammary epithelial cells remain unknown. Therefore, the main aim of the study was to investigate the role of TFEB-mediated autophagy in bovine mammary epithelial cells experiencing oxidative stress. Results H2O2 challenge of the bovine mammary epithelial cell MAC-T increased protein abundance of LC3-II, increased number of autophagosomes and autolysosomes while decreased protein abundance of p62. Inhibition of autophagy via bafilomycin A1 aggravated H2O2-induced reactive oxygen species (ROS) accumulation and apoptosis in MAC-T cells. Furthermore, H2O2 treatment triggered the translocation of TFEB into the nucleus. Knockdown of TFEB by siRNA reversed the effect of H2O2 on protein abundance of LC3-II and p62 as well as the number of autophagosomes and autolysosomes. Overexpression of TFEB activated autophagy and attenuated H2O2-induced ROS accumulation. Furthermore, TFEB overexpression attenuated H2O2-induced apoptosis by downregulating the caspase apoptotic pathway. Conclusions Our results indicate that activation of TFEB mediated autophagy alleviates H2O2-induced oxidative damage by reducing ROS accumulation and inhibiting caspase-dependent apoptosis.

scholarly journals Transition metals activate TFEB in overexpressing cells

2015 ◽  
Vol 470 (1) ◽  
pp. 65-76 ◽  
Author(s):  
Karina A. Peña ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transition Metals ◽  
Mitochondrial Damage ◽  
Cytoprotective Effect ◽  
Transcription Factor Eb

Exposure of cells to micromolar Cu activates recombinant transcription factor EB (TFEB), leading to expression of the lysosomal network genes. Whereas TFEB overexpression has a cytoprotective effect under moderate Cu exposure, it enhances oxidative stress and mitochondrial damage caused by high levels of Cu.

scholarly journals Oxidative Stress Induces Neuronal Apoptosis Through Suppressing Transcription Factor EB Phosphorylation at Ser467

2018 ◽  
Vol 46 (4) ◽  
pp. 1536-1554 ◽  
Author(s):  
Qian Su ◽  
Bin Zheng ◽  
Chen-yao Wang ◽  
Yun-zhi Yang ◽  
Wen-wen Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Cell Apoptosis ◽  
Neuronal Apoptosis ◽  
Nuclear Translocation ◽  
Flow Cytometric Analysis ◽  
Parp Cleavage ◽  
High Concentration ◽  
Akt Inhibitor ◽  
Transcription Factor Eb

Background/Aims: This study determined the role and mechanism of action of transcription factor EB (TFEB) in H2O2-induced neuronal apoptosis. Methods: SH-SY5Y cells were treated with Akt inhibitor/activator and different concentrations of H2O2. Cell apoptosis was detected by flow cytometric analysis. Akt and TFEB phosphorylation and PARP cleavage were determined by Western blotting. HEK293T cells were transfected with different truncated TFEB mutants and HA-Akt-WT; SH-SY5Y cells were transfected with Flag-vector, Flag-TFEB, Flag-TFEB-S467A or Flag-TFEB-S467D; and TFEB interaction with Akt was determined by co-immunoprecipitation and GST pull-down assays. Results: A low concentration of H2O2 induces TFEB phosphorylation at Ser467 and nuclear translocation, facilitating neuronal survival, whereas a high concentration of H2O2 promotes SH-SY5Y cell apoptosis via suppressing TFEB Ser467 phosphorylation and nuclear translocation. The TFEB-S467D mutant is more easily translocated into the nucleus than the non-phosphorylated TFEB-S467A mutant. Further, Akt physically binds to TFEB via its C-terminal tail interaction with the HLH domain of TFEB and phosphorylates TFEB at Ser467. Mutation of TFEB-Ser467 can prevent the phosphorylation of TFEB by Akt, preventing inhibition of oxidative stress-induced apoptosis. Conclusions: Oxidative stress induces neuronal apoptosis through suppressing TFEB phosphorylation at Ser467 by Akt, providing a novel therapeutic strategy for neurodegenerative diseases.

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

Sign in / Sign up

Export Citation Format

Share Document