scholarly journals GPCR transactivation signalling in vascular smooth muscle cells: role of NADPH oxidases and reactive oxygen species

2019 ◽  
Vol 1 (1) ◽  
pp. R1-R11 ◽  
Author(s):  
Raafat Mohamed ◽  
Reearna Janke ◽  
Wanru Guo ◽  
Yingnan Cao ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Drug Targets ◽  
Protein Tyrosine Kinase ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β ◽  
Oxygen Species

The discovery and extension of G-protein-coupled receptor (GPCR) transactivation-dependent signalling has enormously broadened the GPCR signalling paradigm. GPCRs can transactivate protein tyrosine kinase receptors (PTKRs) and serine/threonine kinase receptors (S/TKRs), notably the epidermal growth factor receptor (EGFR) and transforming growth factor-β type 1 receptor (TGFBR1), respectively. Initial comprehensive mechanistic studies suggest that these two transactivation pathways are distinct. Currently, there is a focus on GPCR inhibitors as drug targets, and they have proven to be efficacious in vascular diseases. With the broadening of GPCR transactivation signalling, it is therefore important from a therapeutic perspective to find a common transactivation pathway of EGFR and TGFBR1 that can be targeted to inhibit complex pathologies activated by the combined action of these receptors. Reactive oxygen species (ROS) are highly reactive molecules and they act as second messengers, thus modulating cellular signal transduction pathways. ROS are involved in different mechanisms of GPCR transactivation of EGFR. However, the role of ROS in GPCR transactivation of TGFBR1 has not yet been studied. In this review, we will discuss the involvement of ROS in GPCR transactivation-dependent signalling.

scholarly journals β-Escin alleviates cobalt chloride-induced hypoxia-mediated apoptotic resistance and invasion via ROS-dependent HIF-1α/TGF-β/MMPs in A549 cells

2020 ◽  
Vol 9 (3) ◽  
pp. 191-201
Author(s):  
Chermakani Paneerselvam ◽  
Sudhandiran Ganapasam
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Matrix Metalloproteinases ◽  
Cancer Cells ◽  
Cobalt Chloride ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β ◽  
Oxygen Species

Abstract Hypoxia is contributed in various pathophysiological conditions including obesity, cardiovascular diseases, and cancer. In cancer, hypoxia is a salient phenomenon and has been correlated with tumor progression, metastasis, and provoke resistance to therapies in cancer patients, which exert with stabilization of main effector, hypoxia inducible factor-1 alpha (HIF-1α). Therefore, therapeutic targeting of hypoxic responses in cancer is the potential approach to improve the better treatment efficacy. In the present study, we evaluated the effect of β-Escin (β-Es) on hypoxia-induced resistance to apoptosis and metastasis in human non–small-cell lung cancer cells. The MTT assay revealed that β-Es treatment decreased the A549 cells viability under cobalt chloride-induced hypoxia. Apoptotic proteins were analyzed by western blot that showed cancer cells treated with β-Es induced cell death in hypoxia condition as proteins compared with normoxia. Moreover, we observed that cobalt chloride induced hypoxia through the generation of intracellular reactive oxygen species and stabilized the transcriptional factor HIF-1α, which leads to cancer metastasis. This notion was supported by the migration, invasion, and adhesion assays. Furthermore, hypoxia increased the expression of transforming growth factor-β, and the activation of matrix metalloproteinases were suppressed by the treatment of β-Es as well as pretreatment with N-acetylcysteine (NAC). Therefore, we demonstrate that a concurrent activation of HIF-1α, transforming growth factor-β, and matrix metalloproteinases participate in hypoxia-induced metastasis and that β-Es prevent A549 cells metastasis by inhibition of reactive oxygen species.

Isoform-Specific Activation of Latent Transforming Growth Factor β (LTGF-β) by Reactive Oxygen Species

2006 ◽  
Vol 166 (6) ◽  
pp. 839-848 ◽  
Author(s):  
Michael F. Jobling ◽  
Joni D. Mott ◽  
Monica T. Finnegan ◽  
Vladimir Jurukovski ◽  
Anna C. Erickson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β ◽  
Oxygen Species

Glutathione regulates transforming growth factor-β-stimulated collagen production in fibroblasts

2004 ◽  
Vol 286 (1) ◽  
pp. L121-L128 ◽  
Author(s):  
Rui-Ming Liu ◽  
Yanwen Liu ◽  
Henry Jay Forman ◽  
Mitchell Olman ◽  
Margaret M. Tarpey
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Glucose Oxidase ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β ◽  
Superoxide Production ◽  
Oxygen Species ◽  
Collagen Production

Transforming growth factor-β (TGF-β) is a potent fibrogenic cytokine. The molecular mechanism underlying TGF-β fibrogenesis, however, has not been completely elucidated. In this study, we showed that TGFβ decreased the intracellular GSH content in murine embryo fibroblasts (NIH 3T3), which was followed by an increase in collagen I mRNA content and collagen protein production. Prevention of GSH depletion with N-acetylcysteine (NAC), GSH, or GSH ester abrogated TGF-β-stimulated collagen production, whereas a decrease in intracellular GSH content with l-buthionine- S,R-sulfoximine, an inhibitor of de novo GSH synthesis, enhanced TGF-β-stimulated collagen production. These results suggest that GSH depletion induced by TGF-β may mediate TGF-β-stimulated collagen production. In addition, we showed that TGF-β stimulated superoxide production and increased release of H2O2 from the cells, whereas GSH ester decreased basal and TGF-β + glucose oxidase-stimulated H2O2 release. H2O2, exogenously added or continuously generated by glucose oxidase, enhanced TGF-β-stimulated collagen production, whereas suppression of superoxide production by diphenyliodonium, an NAD(P)H oxidase inhibitor, blocked TGF-β-stimulated collagen production. These data further suggest that reactive oxygen species are involved in TGF-β-stimulated collagen production and that the effect of GSH depletion on TGF-β-stimulated collagen production may be mediated by facilitating reactive oxygen species signaling.

scholarly journals Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-β Signaling

2012 ◽  
Vol 288 (2) ◽  
pp. 770-777 ◽  
Author(s):  
Manu Jain ◽  
Stephanie Rivera ◽  
Elena A. Monclus ◽  
Lauren Synenki ◽  
Aaron Zirk ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species
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