New insights into the role of the Nrf2 signaling pathway in green tea catechin applications

2021 ◽  
Author(s):  
Marjan Talebi ◽  
Mohsen Talebi ◽  
Tahereh Farkhondeh ◽  
Gaurav Mishra ◽  
Selen İlgün ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Green Tea ◽  
Nrf2 Signaling Pathway ◽  
Green Tea Catechin

scholarly journals GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Jingjing Li ◽  
Qiujie Wang ◽  
Yi Yang ◽  
Chong Lei ◽  
Fan Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Aerobic Glycolysis ◽  
Hepatoma Cell ◽  
Related Factor ◽  
Promising Therapeutic Approach ◽  
Nrf2 Signaling Pathway ◽  
Hcc Cells

Abstract Background Glutathione S-transferase zeta 1 (GSTZ1) is the penultimate enzyme in phenylalanine/tyrosine catabolism. GSTZ1 is dysregulated in cancers; however, its role in tumorigenesis and progression of hepatocellular carcinoma (HCC) is largely unknown. We aimed to assess the role of GSTZ1 in HCC and to reveal the underlying mechanisms, which may contribute to finding a potential therapeutic strategy against HCC. Methods We first analyzed GSTZ1 expression levels in paired human HCC and adjacent normal tissue specimens and the prognostic effect of GSTZ1 on HCC patients. Thereafter, we evaluated the role of GSTZ1 in aerobic glycolysis in HCC cells on the basis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Furthermore, we assessed the effect of GSTZ1 on HCC proliferation, glutathione (GSH) concentration, levels of reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (NRF2) signaling via gain- and loss- of GSTZ1 function in vitro. Moreover, we investigated the effect of GSTZ1 on diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) induced hepatocarcinogenesis in a mouse model of HCC. Results GSTZ1 was downregulated in HCC, thus indicating a poor prognosis. GSTZ1 deficiency significantly promoted hepatoma cell proliferation and aerobic glycolysis in HCC cells. Moreover, loss of GSTZ1 function depleted GSH, increased ROS levels, and enhanced lipid peroxidation, thus activating the NRF2-mediated antioxidant pathway. Furthermore, Gstz1 knockout in mice promoted DEN/CCl4-induced hepatocarcinogenesis via activation of the NRF2 signaling pathway. Furthermore, the antioxidant agent N-acetylcysteine and NRF2 inhibitor brusatol effectively suppressed the growth of Gstz1-knockout HepG2 cells and HCC progression in Gstz1−/− mice. Conclusions GSTZ1 serves as a tumor suppressor in HCC. GSH depletion caused by GSTZ1 deficiency elevates oxidative stress, thus constitutively activating the NRF2 antioxidant response pathway and accelerating HCC progression. Targeting the NRF2 signaling pathway may be a promising therapeutic approach for this subset of HCC.

Abstract A066: Role of the NRF2 signaling pathway in sustaining chemoresistance in medulloblastoma

2019 ◽  
Author(s):  
Fatlum Rruga ◽  
Elena Mariotto ◽  
Luca Persano ◽  
Elena Rampazzo ◽  
Alessandra Luchini ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nrf2 Signaling Pathway

scholarly journals Nitro-linoleic acid inhibits vascular smooth muscle cell proliferation via the Keap1/Nrf2 signaling pathway

2007 ◽  
Vol 293 (1) ◽  
pp. H770-H776 ◽  
Author(s):  
Luis Villacorta ◽  
Jifeng Zhang ◽  
Minerva T. Garcia-Barrio ◽  
Xi-lin Chen ◽  
Bruce A. Freeman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Linoleic Acid ◽  
Vascular Smooth Muscle ◽  
Signaling Pathway ◽  
Related Factor ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Vsmc Proliferation ◽  
Nrf2 Signaling Pathway

Nitroalkenes, the nitration products of unsaturated fatty acids formed via NO-dependent oxidative reactions, have been demonstrated to exert strong biological actions in endothelial cells and monocytes/macrophages; however, little is known about their effects on vascular smooth muscle cells (VSMCs). The present study examined the role of nitro-linoleic acid (LNO2) in the regulation of VSMC proliferation. We observed that LNO2 inhibited VSMC proliferation in a dose-dependent manner. In addition, LNO2 induced growth arrest of VSMCs in the G1/S phase of the cell cycle with an upregulation of the cyclin-dependent kinase inhibitor p27kip1. Furthermore, LNO2 triggered nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation and activation of the antioxidant-responsive element-driven transcriptional activity via impairing Kelch-like ECH-associating protein 1 (Keap1)-mediated negative control of Nrf2 activity in VSMCs. LNO2 upregulated the expression of Nrf2 protein levels, but not mRNA levels, in VSMCs. A forced activation of Nrf2 led to an upregulation of p27kip1 and growth inhibition of VSMCs. In contrast, knock down of Nrf2 using an Nrf2 siRNA approach reversed the LNO2-induced upregulation of p27kip1 and inhibition of cellular proliferation in VSMCs. These studies provide the first evidence that nitroalkene LNO2 inhibits VSMC proliferation through activation of the Keap1/Nrf2 signaling pathway, suggesting an important role of nitroalkenes in vascular biology.

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