Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens

2012 ◽  
Vol 133 (11-12) ◽  
pp. 665-674 ◽  
Author(s):  
Lixin Wang ◽  
Julie A. Eldred ◽  
Peter Sidaway ◽  
Julie Sanderson ◽  
Andrew J.O. Smith ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Er Stress ◽  
Stress Responses ◽  
Human Lens ◽  
Receptor Stimulation ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals Sigma-1 Receptor Promotes Mitochondrial Bioenergetics by Orchestrating ER Ca2+ Leak during Early ER Stress

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 422
Author(s):  
Zhanat Koshenov ◽  
Furkan E. Oflaz ◽  
Martin Hirtl ◽  
Johannes Pilic ◽  
Olaf A. Bachkoenig ◽  
...  
Keyword(s):  
Er Stress ◽  
Energy Demand ◽  
Molecular Mechanisms ◽  
High Energy ◽  
Human Neuroblastoma Cell ◽  
Mitochondrial Bioenergetics ◽  
Dependent Manner ◽  
Human Neuroblastoma ◽  
Sigma 1 Receptor ◽  
Sigma 1

The endoplasmic reticulum (ER) is a complex, multifunctional organelle of eukaryotic cells and responsible for the trafficking and processing of nearly 30% of all human proteins. Any disturbance to these processes can cause ER stress, which initiates an adaptive mechanism called unfolded protein response (UPR) to restore ER functions and homeostasis. Mitochondrial ATP production is necessary to meet the high energy demand of the UPR, while the molecular mechanisms of ER to mitochondria crosstalk under such stress conditions remain mainly enigmatic. Thus, better understanding the regulation of mitochondrial bioenergetics during ER stress is essential to combat many pathologies involving ER stress, the UPR, and mitochondria. This article investigates the role of Sigma-1 Receptor (S1R), an ER chaperone, has in enhancing mitochondrial bioenergetics during early ER stress using human neuroblastoma cell lines. Our results show that inducing ER stress with tunicamycin, a known ER stressor, greatly enhances mitochondrial bioenergetics in a time- and S1R-dependent manner. This is achieved by enhanced ER Ca2+ leak directed towards mitochondria by S1R during the early phase of ER stress. Our data point to the importance of S1R in promoting mitochondrial bioenergetics and maintaining balanced H2O2 metabolism during early ER stress.

At the Crossing of ER Stress and MAMs: A Key Role of Sigma-1 Receptor?

2019 ◽  
pp. 699-718 ◽  
Author(s):  
Benjamin Delprat ◽  
Lucie Crouzier ◽  
Tsung-Ping Su ◽  
Tangui Maurice
Keyword(s):  
Er Stress ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

2020 ◽  
Vol 11 ◽  
Author(s):  
José Miguel Vela
Keyword(s):  
Stress Response ◽  
Viral Replication ◽  
Er Stress ◽  
Host Cell ◽  
Drug Repurposing ◽  
Host Protein ◽  
Unique Challenge ◽  
Sigma 1 Receptor ◽  
Sigma 1

Outbreaks of emerging infections, such as COVID-19 pandemic especially, confront health professionals with the unique challenge of treating patients. With no time to discover new drugs, repurposing of approved drugs or in clinical development is likely the only solution. Replication of coronaviruses (CoVs) occurs in a modified membranous compartment derived from the endoplasmic reticulum (ER), causes host cell ER stress and activates pathways to facilitate adaptation of the host cell machinery to viral needs. Accordingly, modulation of ER remodeling and ER stress response might be pivotal in elucidating CoV-host interactions and provide a rationale for new therapeutic, host-based antiviral approaches. The sigma-1 receptor (Sig-1R) is a ligand-operated, ER membrane-bound chaperone that acts as an upstream modulator of ER stress and thus a candidate host protein for host-based repurposing approaches to treat COVID-19 patients. Sig-1R ligands are frequently identified in in vitro drug repurposing screens aiming to identify antiviral compounds against CoVs, including severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Sig-1R regulates key mechanisms of the adaptive host cell stress response and takes part in early steps of viral replication. It is enriched in lipid rafts and detergent-resistant ER membranes, where it colocalizes with viral replicase proteins. Indeed, the non-structural SARS-CoV-2 protein Nsp6 interacts with Sig-1R. The activity of Sig-1R ligands against COVID-19 remains to be specifically assessed in clinical trials. This review provides a rationale for targeting Sig-1R as a host-based drug repurposing approach to treat COVID-19 patients. Evidence gained using Sig-1R ligands in unbiased in vitro antiviral drug screens and the potential mechanisms underlying the modulatory effect of Sig-1R on the host cell response are discussed. Targeting Sig-1R is not expected to reduce dramatically established viral replication, but it might interfere with early steps of virus-induced host cell reprogramming, aid to slow down the course of infection, prevent the aggravation of the disease and/or allow a time window to mature a protective immune response. Sig-1R-based medicines could provide benefit not only as early intervention, preventive but also as adjuvant therapy.

Dehydroepiandrosterone administration improves memory deficits following transient brain ischemia through sigma-1 receptor stimulation

2015 ◽  
Vol 1622 ◽  
pp. 102-113 ◽  
Author(s):  
Yasushi Yabuki ◽  
Yasuharu Shinoda ◽  
Hisanao Izumi ◽  
Tatuya Ikuno ◽  
Norifumi Shioda ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
Memory Deficits ◽  
Receptor Stimulation ◽  
Sigma 1 Receptor ◽  
Sigma 1
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