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 Dual Aquaporin and Sigma1 Receptor (DAS) Modulators: New Tools for Counteracting Oxidative Stress

2020 ◽  
Author(s):  
Giorgia Pellavio ◽  
Giacomo Rossino ◽  
Giulia Gastaldi ◽  
Daniela Rossi ◽  
Pasquale Linciano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Small Molecules ◽  
Water Permeability ◽  
Hela Cells ◽  
Oxygen Species ◽  
Degenerative Diseases ◽  
Relevant Role ◽  
Stressed Cells ◽  
Innovative Drugs ◽  
Sigma1 Receptor

Specific aquaporins (AQP), called peroxyporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasting during oxidative stress. Another target involved in oxidative stress is the Sigma1 Receptor (S1R), since its activation is triggered by oxidative or endoplasmic reticulum stress. Herein we evaluated the effect of S1R modulators on AQP-dependent water 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. All compounds except one were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together, our results support the hypothesis that the investigated compounds act as dual aquaporin and Sigma1 receptor (DAS) modulators. The finding that small molecules can modulate both AQP and S1R opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, like cancer and degenerative diseases.

scholarly journals The sigma-1 receptor-zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury

2016 ◽  
Vol 105 ◽  
pp. 1-9 ◽  
Author(s):  
Tzu-Chieh Su ◽  
Shu-Hui Lin ◽  
Pin-Tse Lee ◽  
Shiu-Hwa Yeh ◽  
Tsung-Hsun Hsieh ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Zinc Finger ◽  
Cell Injury ◽  
Zinc Finger Protein ◽  
Sigma 1 Receptor ◽  
Finger Protein ◽  
Sigma 1

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

scholarly journals Sigma-1 receptor is a key genetic modulator in amyotrophic lateral sclerosis

2019 ◽  
Author(s):  
Simon Couly ◽  
Bilal Khalil ◽  
Véronique Viguier ◽  
Julien Roussel ◽  
Tangui Maurice ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
High Energy ◽  
Dependent Manner ◽  
Wild Type ◽  
Sigma 1 Receptor ◽  
Atp Levels ◽  
Sigma 1 ◽  
Lateral Sclerosis

Abstract Sigma-1 receptor (S1R) is an endoplasmic reticulum (ER) chaperone that regulates mitochondrial respiration but also controls cellular defense against ER and oxidative stress. This makes S1R a potential therapeutic target in amyotrophic lateral sclerosis (ALS). Especially, as a missense mutation E102Q in S1R has been reported in few familial ALS cases. However, the pathogenicity of S1RE102Q and the beneficial impact of S1R in the ALS context remain to be demonstrated in vivo. To address this, we generated transgenic Drosophila that express human wild-type S1R or S1RE102Q. Expression of mutant S1R in fly neurons induces abnormal eye morphology and locomotor defects in a dose-dependent manner. This was accompanied by abnormal mitochondrial fragmentation, reduced ATP levels and a higher fatigability at the neuromuscular junction during high energy demand. Overexpressing IP3 receptor or glucose transporter mitigates the S1RE102Q-induced eye phenotype, further highlighting the role of calcium and energy metabolism in its toxicity. More importantly, we showed that wild-type S1R rescues locomotor activity and ATP levels of flies expressing the key ALS protein, TDP43. Moreover, overexpressing wild-type S1R enhances resistance of flies to oxidative stress. Therefore, our data provide the first genetic evidence that mutant S1R recapitulates ALS pathology in vivo while increasing S1R confers neuroprotection against TDP43 toxicity.

scholarly journals Effect of ethanol on hydrogen peroxide-induced AMPK phosphorylation

2008 ◽  
Vol 295 (6) ◽  
pp. G1173-G1181 ◽  
Author(s):  
Suthat Liangpunsakul ◽  
Sung-Eun Wou ◽  
Yan Zeng ◽  
Ruth A. Ross ◽  
Hiremagalur N. Jayaram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Okadaic Acid ◽  
Hela Cells ◽  
Inhibitory Effect ◽  
Hepatoma Cells ◽  
Small Interference Rna ◽  
Ampk Phosphorylation ◽  
Phosphatase 2A ◽  
Pkc Ζ

AMP-activated protein kinase (AMPK) responds to oxidative stress. Previous work has shown that ethanol treatment of cultured hepatoma cells and of mice inhibited the activity of AMPK and reduced the amount of AMPK protein. Ethanol generates oxidative stress in the liver. Since AMPK is activated by reactive oxygen species, it seems paradoxical that ethanol would inhibit AMPK in the hepatoma cells. In an attempt to understand the mechanism whereby ethanol inhibits AMPK, we studied the effect of ethanol on AMPK activation by exogenous hydrogen peroxide. The effects of ethanol, hydrogen peroxide, and inhibitors of protein phosphatase 2A (PP2A) [either okadaic acid or PP2A small interference RNA (siRNA)] on AMPK phosphorylation and activity were examined in rat hepatoma cells (H4IIEC3) and HeLa cells. In H4IIEC3 cells, hydrogen peroxide (H2O2, 1 mM) transiently increased the level of phospho-AMPK to 1.5-fold over control ( P < 0.05). Similar findings were observed in HeLa cells, which do not express the upstream AMPK kinase, LKB1. H2O2 markedly increased the phosphorylation of LKB1 in H4IIEC3 cells. Ethanol significantly inhibited the phosphorylation of PKC-ζ, LKB1, and AMPK caused by exposure to H2O2. This inhibitory effect of ethanol required its metabolism. More importantly, the inhibitory effects of ethanol on H2O2-induced AMPK phosphorylation were attenuated by the presence of the PP2A inhibitor, okadaic acid, or PP2A siRNA. The inhibitory effect of ethanol on AMPK phosphorylation is exerted through the inhibition of PKC-ζ and LKB1 phosphorylation and the activation of PP2A.

[123I]TPCNE: A novel SPET tracer for the sigma-1 receptor binds irreversibly in humans in vivo

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S655-S655
Author(s):  
James M Stone ◽  
Erik Arstad ◽  
Kjell Erlandsson ◽  
Rikki N Waterhouse ◽  
Peter J Ell ◽  
...  
Keyword(s):  
Sigma 1 Receptor ◽  
Sigma 1
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