Antimony, a novel nerve poison, triggers neuronal autophagic death via reactive oxygen species-mediated inhibition of the protein kinase B/mammalian target of rapamycin pathway

2019 ◽  
Vol 114 ◽  
pp. 105561 ◽  
Author(s):  
Xiaoke Wang ◽  
Piaoyu Zhu ◽  
Shenya Xu ◽  
Yuting Liu ◽  
Yang Jin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Reactive Oxygen ◽  
Target Of Rapamycin ◽  
Oxygen Species

scholarly journals Enhanced c-Met activity promotes G-CSF–induced mobilization of hematopoietic progenitor cells via ROS signaling

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 419-428 ◽  
Author(s):  
Melania Tesio ◽  
Karin Golan ◽  
Simona Corso ◽  
Silvia Giordano ◽  
Amir Schajnovitz ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Reactive Oxygen ◽  
Target Of Rapamycin ◽  
Oxygen Species ◽  
Hematopoietic Progenitor ◽  
Stromal Cell Derived Factor

Abstract Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor–induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell–derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1+/c-Kit+/Lin− cells and interfered with their enhanced chemotactic migration to stromal cell–derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met–mediated mobilization. Our data show dynamic c-Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms.

scholarly journals Protein Kinase B Activation by Reactive Oxygen Species Is Independent of Tyrosine Kinase Receptor Phosphorylation and Requires Src Activity

2003 ◽  
Vol 278 (23) ◽  
pp. 20828-20834 ◽  
Author(s):  
Franca Esposito ◽  
Giuseppa Chirico ◽  
Nicola Montesano Gesualdi ◽  
Inmaculada Posadas ◽  
Rosario Ammendola ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Kinase B ◽  
Reactive Oxygen ◽  
Tyrosine Kinase Receptor ◽  
Oxygen Species ◽  
Receptor Phosphorylation

scholarly journals Activation of Autophagic Flux against Xenoestrogen Bisphenol-A-induced Hippocampal Neurodegeneration via AMP kinase (AMPK)/Mammalian Target of Rapamycin (mTOR) Pathways

2015 ◽  
Vol 290 (34) ◽  
pp. 21163-21184 ◽  
Author(s):  
Swati Agarwal ◽  
Shashi Kant Tiwari ◽  
Brashket Seth ◽  
Anuradha Yadav ◽  
Anshuman Singh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Bisphenol A ◽  
Mammalian Target Of Rapamycin ◽  
Reactive Oxygen ◽  
Target Of Rapamycin ◽  
Autophagic Flux ◽  
Compensatory Mechanism ◽  
Oxygen Species ◽  
Amp Kinase

The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA-induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down-regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell's compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure.

Mammalian target of rapamycin mediates the angiogenic effects of leptin in human hepatic stellate cells

2011 ◽  
Vol 301 (2) ◽  
pp. G210-G219 ◽  
Author(s):  
Sara Aleffi ◽  
Nadia Navari ◽  
Wanda Delogu ◽  
Sara Galastri ◽  
Erica Novo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatic Stellate Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Mammalian Target Of Rapamycin ◽  
Reactive Oxygen ◽  
Stellate Cells ◽  
Target Of Rapamycin ◽  
Oxygen Species ◽  
Diphenylene Iodonium

Leptin modulates the angiogenic properties of hepatic stellate cells (HSC), but the molecular mechanisms involved are poorly understood. We investigated the pathways regulating hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in leptin-stimulated myofibroblastic HSC. Exposure to leptin enhanced the phosphorylation of TSC2 on T1462 residues and of p70 S6 kinase and the translational inhibitor 4E-binding protein-1, indicating the ability of leptin to activate the mammalian target of rapamycin (mTOR) pathway. Similar findings were observed when HSC were exposed to PDGF. Both leptin and PDGF increased the expression of HIF-1α and VEGF in HSC. In the presence of rapamycin, a specific mTOR inhibitor, leptin and PDGF were no longer able to activate mTOR, and expression of VEGF was reduced, whereas HIF-1α abundance was not affected. Moreover, knockdown of Raptor, a component of the mTORC1 complex, reduced the ability of leptin to increase VEGF. mTOR was also necessary for leptin- and PDGF-dependent increase in HSC migration. Leptin increased the generation of reactive oxygen species in HSC, which was reduced by NADP(H) oxidase inhibitors. Both N-acetyl cysteine and diphenylene iodonium, a NADP(H) inhibitor, inhibited the expression of HIF-1α and VEGF stimulated by leptin or PDGF. Finally, conditioned media from HSC treated with leptin or PDGF induced tube formation in cultured human umbilical vein endothelial cells. In conclusion, in HSC exposed to leptin or PDGF, increased expression of VEGF requires both activation of mTOR and generation of reactive oxygen species via NADPH-oxidase. Induction of HIF-1α requires NADP(H) oxidase but not mTOR activation.

scholarly journals Ceramide and Reactive Oxygen Species Generated by H2O2Induce Caspase-3-independent Degradation of Akt/Protein Kinase B

2002 ◽  
Vol 277 (45) ◽  
pp. 42943-42952 ◽  
Author(s):  
Daniel Martı́n ◽  
Marta Salinas ◽  
Naoya Fujita ◽  
Takashi Tsuruo ◽  
Antonio Cuadrado
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Caspase 3 ◽  
Protein Kinase B ◽  
Reactive Oxygen ◽  
Oxygen Species
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