scholarly journals Sigma-1 receptor is involved in diminished ovarian reserve possibly by influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis

Aging ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 9041-9065
Author(s):  
Lile Jiang ◽  
Jinquan Cui ◽  
Cuilian Zhang ◽  
Juanke Xie ◽  
Shaodi Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Granulosa Cells ◽  
Ovarian Reserve ◽  
Diminished Ovarian Reserve ◽  
Sigma 1 Receptor ◽  
Sigma 1

Protective effect of a novel sigma-1 receptor agonist is associated with reduced endoplasmic reticulum stress in stroke male mice

2018 ◽  
Vol 96 (10) ◽  
pp. 1707-1716 ◽  
Author(s):  
Ryuta Morihara ◽  
Toru Yamashita ◽  
Xia Liu ◽  
Yumiko Nakano ◽  
Yusuke Fukui ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Receptor Agonist ◽  
Male Mice ◽  
Sigma 1 Receptor ◽  
Sigma 1

Pridopidine reduces mutant huntingtin‐induced endoplasmic reticulum stress by modulation of the Sigma‐1 receptor

2021 ◽  
Author(s):  
Marina Shenkman ◽  
Michal Geva ◽  
Noga Gershoni‐Emek ◽  
Michael R. Hayden ◽  
Gerardo Z. Lederkremer
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mutant Huntingtin ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition

2021 ◽  
Author(s):  
Mohamed Omar Taqi ◽  
Mohammed Saeed-Zidane ◽  
Samuel Gebremedhn ◽  
Dessie Salilew-Wondim ◽  
Ernst Tholen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Transcription Factors ◽  
Endoplasmic Reticulum Stress ◽  
Granulosa Cells ◽  
Mitochondrial Activity ◽  
Small Interference Rna ◽  
Nrf2 Signaling Pathway

AbstractTranscription factors (TFs) are known to be involved in regulating the expression of several classes of genes during folliculogenesis. However, the regulatory role of TFs during oxidative stress (OS) is not fully understood. The current study was aimed to investigate the regulation of the TFs in bovine granulosa cells (bGCs) during exposure to OS induced by H2O2 in vitro. For this, bGCs derived from ovarian follicles were cultured in vitro till their confluency and then treated with H2O2 for 40 min. Twenty-four hours later, cells were subjected to various phenotypic and gene expression analyses for genes related to TFs, endoplasmic reticulum stress, apoptosis, cell proliferation, and differentiation markers. The bGCs exhibited higher reactive oxygen species accumulation, DNA fragmentation, and endoplasmic reticulum stress accompanied by reduction of mitochondrial activity after exposure to OS. In addition, higher lipid accumulation and lower cell proliferation were noticed in H2O2-challenged cells. The mRNA level of TFs including NRF2, E2F1, KLF6, KLF9, FOS, SREBF1, SREBF2, and NOTCH1 was increased in H2O2-treated cells compared with non-treated controls. However, the expression level of KLF4 and its downstream gene, CCNB1, were downregulated in the H2O2-challenged group. Moreover, targeted inhibition of NRF2 using small interference RNA resulted in reduced expression of KLF9, FOS, SREBF2, and NOTCH1 genes, while the expression of KLF4 was upregulated. Taken together, bovine granulosa cells exposed to OS exhibited differential expression of various transcription factors, which are mediated by the NRF2 signaling pathway.

scholarly journals Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110265
Author(s):  
Vladimir Zhemkov ◽  
Jen Liou ◽  
Ilya Bezprozvanny
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Composition ◽  
Sigma 1 Receptor ◽  
Functional Roles ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Sigma 1 ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Cellular Organelles

Recent studies indicated potential importance of membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other cellular organelles. These MCS have unique protein and lipid composition and serve as hubs for inter-organelle communication and signaling. Despite extensive investigation of MCS protein composition and functional roles, little is known about the process of MCS formation. In this perspective, we propose a hypothesis that MCS are formed not as a result of random interactions between membranes of ER and other organelles but on the basis of pre-existing cholesterol-enriched ER microdomains.

The sigma 1 receptor (S1R) is a potential therapeutic target for the treatment of Huntington's disease

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Endoplasmic Reticulum ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Therapeutic Target ◽  
Structural Integrity ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Potential Therapeutic Target ◽  
Sigma 1 Receptor ◽  
Sigma 1

During the progression of Huntington's disease (HD), changes in Ca2+ signaling cause neuronal cells to lose a range of functional properties. GABAergic medium spiny neurons (MSNs) are able to prevent Ca2+ imbalance in the early stages of the illness through a number of compensatory strategies. However, as people become older, their neuroprotective potential diminishes due to a decrease in metabolic activity and the generation of Ca2+-buffering proteins. Continuing Ca2+ regulation problems exhaust the cells' compensatory abilities, resulting in a continuous surge in cytosolic Ca2+ and neuronal degeneration.The sigma 1 receptor (S1R) is a potential therapeutic target for the treatment of HD because it regulates a number of cytosolic Ca2+-dependent signaling cascades. S1R activation by selective agonists protects neurons from glutamate excitotoxicity, reduces store-operated Ca2+ entry (SOCE) hyperactivation, and maintains the structural integrity of mitochondria-associated endoplasmic reticulum membranes (MAMs), which is required for synchronizing mitochondrial and endoplasmic reticulum (ER) activity to maintain cell bioenergetics balance. Because of the stability of Ca2+ signaling in neurons, pridopidine, a highly selective S1R agonist, has been demonstrated to protect neurons in cellular and animal models of HD.The synaptoprotective effect of pridopidine is very important since it is found in both cortical and striatal neurons, indicating that pridopidine has a systemic influence on HD therapy. Because synaptic dysfunctions are one of the earliest markers of neuropathology at the cellular level, normalization of Ca2+ balance by pridopidine may prevent disease development at the molecular level at the earliest stages. In this regard, the most significant therapeutic advantage of pridopidine will almost certainly be in preventative treatment, even before the start of the first clinical indications, which will improve neuronal cell compensatory abilities and significantly reduce the progression of HD.

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