scholarly journals The sigma-1 receptor protects against cellular oxidative stress and activates antioxidant response elements

2012 ◽  
Vol 682 (1-3) ◽  
pp. 12-20 ◽  
Author(s):  
Arindam Pal ◽  
Dominique Fontanilla ◽  
Anupama Gopalakrishnan ◽  
Young-Kee Chae ◽  
John L. Markley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Response ◽  
Sigma 1 Receptor ◽  
Response Elements ◽  
Sigma 1 ◽  
Antioxidant Response Elements

ZFARED: A Database of the Antioxidant Response Elements in Zebrafish

2020 ◽  
Vol 15 (5) ◽  
pp. 415-419
Author(s):  
Azhwar Raghunath ◽  
Raju Nagarajan ◽  
Ekambaram Perumal
Keyword(s):  
Target Genes ◽  
Antioxidant Response ◽  
Zebrafish Genome ◽  
Promoter Regions ◽  
Protein Coding ◽  
Response Elements ◽  
Toxic Agents ◽  
Upstream Promoter ◽  
Its Gene ◽  
Antioxidant Response Elements

Background: Antioxidant Response Elements (ARE) play a key role in the expression of Nrf2 target genes by regulating the Keap1-Nrf2-ARE pathway, which offers protection against toxic agents and oxidative stress-induced diseases. Objective: To develop a database of putative AREs for all the genes in the zebrafish genome. This database will be helpful for researchers to investigate Nrf2 regulatory mechanisms in detail. Methods: To facilitate researchers functionally characterize zebrafish AREs, we have developed a database of AREs, Zebrafish Antioxidant Response Element Database (ZFARED), for all the protein-coding genes including antioxidant and mitochondrial genes in the zebrafish genome. The front end of the database was developed using HTML, JavaScript, and CSS and tested in different browsers. The back end of the database was developed using Perl scripts and Perl-CGI and Perl- DBI modules. Results: ZFARED is the first database on the AREs in zebrafish, which facilitates fast and efficient searching of AREs. AREs were identified using the in-house developed Perl algorithms and the database was developed using HTML, JavaScript, and Perl-CGI scripts. From this database, researchers can access the AREs based on chromosome number (1 to 25 and M for mitochondria), strand (positive or negative), ARE pattern and keywords. Users can also specify the size of the upstream/promoter regions (5 to 30 kb) from transcription start site to access the AREs located in those specific regions. Conclusion: ZFARED will be useful in the investigation of the Keap1-Nrf2-ARE pathway and its gene regulation. ZFARED is freely available at http://zfared.buc.edu.in/.

scholarly journals Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yasuhiro Nakagami
Keyword(s):  
Oxidative Stress ◽  
Neuronal Degeneration ◽  
Antioxidant Response ◽  
Related Factor ◽  
Retinal Diseases ◽  
Age Related ◽  
Nrf2 Signaling Pathway ◽  
Genes Encoding ◽  
Antioxidant Response Elements ◽  
Nrf2 Activator

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many species. The retina is constantly exposed to reactive oxygen species, and oxidative stress is a major contributor to age-related macular diseases. Moreover, the resulting inflammation and neuronal degeneration are also related to other retinal diseases. The well-known Nrf2 activators, bardoxolone methyl and its derivatives, have been the subject of a number of clinical trials, including those aimed at treating chronic kidney disease, pulmonary arterial hypertension, and mitochondrial myopathies. Recent studies suggest that Nrf2 activation protects the retina from retinal diseases. In particular, this is supported by the finding that Nrf2 knockout mice display age-related retinal degeneration. Moreover, the concept has been validated by the efficacy of Nrf2 activators in a number of retinal pathological models. We have also recently succeeded in generating a novel Nrf2 activator, RS9, using a biotransformation technique. This review discusses current links between retinal diseases and Nrf2 and the possibility of treating retinal diseases by activating the Nrf2 signaling pathway.

scholarly journals Nestin regulates cellular redox homeostasis in lung cancer through the Keap1–Nrf2 feedback loop

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiancheng Wang ◽  
Qiying Lu ◽  
Jianye Cai ◽  
Yi Wang ◽  
Xiaofan Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Feedback Loop ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Cellular Redox ◽  
Anti Cancer ◽  
Oxidative Stress Status ◽  
Kelch Domain ◽  
Antioxidant Response Elements

Abstract Abnormal cancer antioxidant capacity is considered as a potential mechanism of tumor malignancy. Modulation of oxidative stress status is emerging as an anti-cancer treatment. Our previous studies have found that Nestin-knockdown cells were more sensitive to oxidative stress in non-small cell lung cancer (NSCLC). However, the molecular mechanism by which Nestin protects cells from oxidative damage remains unclear. Here, we identify a feedback loop between Nestin and Nrf2 maintaining the redox homeostasis. Mechanistically, the ESGE motif of Nestin interacts with the Kelch domain of Keap1 and competes with Nrf2 for Keap1 binding, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant enzyme generation. Interestingly, we also map that the antioxidant response elements (AREs) in the Nestin promoter are responsible for its induction via Nrf2. Taken together, our results indicate that the Nestin–Keap1–Nrf2 axis regulates cellular redox homeostasis and confers oxidative stress resistance in NSCLC.

scholarly journals Sigma-1 Receptor Agonists Acting on Aquaporin-Mediated H2O2 Permeability: New Tools for Counteracting Oxidative Stress

2021 ◽  
Vol 22 (18) ◽  
pp. 9790
Author(s):  
Giorgia Pellavio ◽  
Giacomo Rossino ◽  
Giulia Gastaldi ◽  
Daniela Rossi ◽  
Pasquale Linciano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Water Permeability ◽  
Hela Cells ◽  
Sigma 1 Receptor ◽  
Antioxidant Mechanism ◽  
Sigma 1 ◽  
Relevant Role ◽  
Stressed Cells ◽  
Innovative Drugs

Sigma1 Receptor (S1R) is involved in oxidative stress, since its activation is triggered by oxidative or endoplasmic reticulum stress. Since specific aquaporins (AQP), called peroxiporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasted during oxidative stress, we studied the effect of S1R modulators on AQP-dependent water and hydrogen peroxide permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in HeLa cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. Moreover, compounds were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together these results support the hypothesis that the antioxidant mechanism is mediated by both S1R and AQP-mediated H2O2 permeability. The finding that small molecules can act on both S1R and AQP-mediated H2O2 permeability opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, such as cancer and degenerative diseases.

scholarly journals Haem oxygenase-1 up-regulation by rosiglitazone via ROS-dependent Nrf2-antioxidant response elements axis or PPARγ attenuates LPS-mediated lung inflammation

2018 ◽  
Vol 175 (20) ◽  
pp. 3928-3946 ◽  
Author(s):  
Rou-Ling Cho ◽  
Chien-Chung Yang ◽  
Hui-Ching Tseng ◽  
Li-Der Hsiao ◽  
Chih-Chung Lin ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Antioxidant Response ◽  
Response Elements ◽  
Antioxidant Response Elements ◽  
Haem Oxygenase

Genome-wide identification and analysis of Nrf2 binding sites – Antioxidant response elements in zebrafish

2018 ◽  
Vol 360 ◽  
pp. 236-248 ◽  
Author(s):  
Azhwar Raghunath ◽  
Raju Nagarajan ◽  
Kiruthika Sundarraj ◽  
Lakshmikanthan Panneerselvam ◽  
Ekambaram Perumal
Keyword(s):  
Binding Sites ◽  
Antioxidant Response ◽  
Response Elements ◽  
Genome Wide ◽  
Antioxidant Response Elements

scholarly journals Identification of polymorphic antioxidant response elements in the human genome

2007 ◽  
Vol 16 (22) ◽  
pp. 2780-2780 ◽  
Author(s):  
X. Wang ◽  
D. J. Tomso ◽  
B. N. Chorley ◽  
H.-Y. Cho ◽  
V. G. Cheung ◽  
...  
Keyword(s):  
Human Genome ◽  
Antioxidant Response ◽  
Response Elements ◽  
Antioxidant Response Elements
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