MicroRNA-297 promotes cardiomyocyte hypertrophy via targeting sigma-1 receptor

Life Sciences ◽  
2017 ◽  
Vol 175 ◽  
pp. 1-10 ◽  
Author(s):  
Qinxue Bao ◽  
Mingyue Zhao ◽  
Li Chen ◽  
Yu Wang ◽  
Siyuan Wu ◽  
...  
Keyword(s):  
Cardiomyocyte Hypertrophy ◽  
Sigma 1 Receptor ◽  
Sigma 1

Abstract 249: Sigma-1 Receptor Agonist Ameliorates Mitochondrial ATP Production and Apoptosis in Cardiac Myocytes

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Hideaki Tagashira ◽  
Norifumi Shioda ◽  
Md. Shenuarin Bhuiyan ◽  
Kohji Fukunaga
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Intracellular Localization ◽  
Receptor Expression ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Ang Ii ◽  
Receptor Stimulation ◽  
Sigma 1 Receptor ◽  
Atp Production ◽  
Sigma 1

Objective: Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post-myocardial infarction (MI)-induced morbidity and mortality. However, the molecular mechanism underlying SSRI-induced cardioprotection remains unclear. We previous reported that fluvoxamine with high affinity for sigma-1 receptor ameliorates cardiac hypertrophy and dysfunction via sigma-1 receptor stimulation. In non-cardiomyocytes, sigma-1 receptor interacts with IP 3 receptor (IP 3 R), which may promote Ca 2+ transport to mitochondria. We here investigated the role of sigma-1 receptor for sarcoplasmic reticulum (SR)-mitochondrial Ca 2+ signaling in neonatal rat ventricular cardiomyocytes. Methods: Cultured cardiomyocytes were treated with angiotensin II (Ang II) during 72 hr followed by fluvoxamine and/or NE-100 treatment during the last 24 hr. Then, we investigated intracellular localization of sigma-1 receptor and IP 3 R. We also measured phenylephrine (PE)-induced mitochondrial Ca 2+ and cytosolic Ca 2+ mobilization and ATP content in Ang II-treated cardiomyocytes with or without fluvoxamine treatments. Results: Ang II stimulation for 72 hr elicited cardiomyocyte hypertrophy, downregulation of sigma-1 receptor expression and declined PE-induced Ca 2+ mobilization into cytosol and mitochondria. Fluvoxamine treatments restored sigma-1 receptor expression and PE-induced Ca 2+ mobilization into mitochondria. Moreover, fluvoxamine treatment completely restored Ang II-induced apoptosis. We also confirmed in vivo that fluvoxamine treatment rescue transverse aortic constriction-induced cardiac dysfunction and the reduced ATP concentration. Conclusions: These results suggested that fluvoxamine rescue cardiomyocytes from AngII-induced cardiac myocyte apoptosis through enhancement of SR-mitochondria Ca 2+ transport and mitochondrial ATP production via sigma-1 receptor stimulation.

Abstract 4: The Mitochondrial Ca 2+ Transport and ATP Production Through Sigma-1 Receptor in Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Kohji Fukunaga ◽  
Hideaki Tagashira
Keyword(s):  
Cardiac Dysfunction ◽  
Receptor Agonist ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Ang Ii ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Sigma 1 Receptor ◽  
Atp Production ◽  
Sigma 1

Objective: Although sigma-1 receptor is originally postulated as an opioid receptor in the central nervous system, we recently defined the higher expression of sigma-1 receptor in cardiac ventricle and kidney as compared to brain tissues (Expert Opin Ther Targets 2010;14:1009-1022). To address the question whether mitochondrial Ca 2+ transport and ATP production in heart are regulated by sigma-1 receptor stimulation, we tested the anti-hypertrophic effects of the specific sigma-1 receptor agonist, SA4503 in transverse aortic constriction (TAC) mice. Methods: We treated mice with SA4503 (0.1, 0.3 and 1.0 mg/kg) orally once a day for 4 weeks after TAC. The cardiac constriction was monitored by echocardiography. The mitochondrial Ca 2+ transport and ATP production with or without SA4503 treatment were measured in cultured neonatal cardiomyocytes. Results: The sigma-1 receptor expression in the left ventricle (LV) decreased significantly over the 4 weeks. SA4503 administration significantly attenuated TAC-induced myocardial hypertrophy concomitant with the recovery of sigma-1 receptor expression in LV. SA4503 also ameliorated the impaired LV fractional shortening. We also investigated the role of sigma-1 receptor for sarcoplasmic reticulum (SR)-mitochondrial Ca 2+ transport in cultured neonatal rat ventricular cardiomyocytes. Exposure to angiotensin II (Ang II) for 72 hr elicited marked cardiomyocyte hypertrophy and declined phenylephrine (PE)-induced Ca 2+ mobilization into cytosol and mitochondria. SA4503 treatment restored significantly the reduced PE-induced Ca 2+ mobilization into mitochondria. Importantly, The Ang II-induced hypertrophy in vitro and transverse aortic constriction-induced cardiac dysfunction in vivo were associated with the reduced ATP concentration, which was completely restored by SA4503 treatment. NE-100, a sigma-1 receptor selective antagonist, abolished these effects induced by SA4503. Conclusion: The specific sigma-1 receptor agonist, SA4503 ameliorates AngII-induced cardiomyocyte hypertrophy and TAC-induced cardiac dysfunction through restoration of SR-mitochondria Ca 2+ transport via sigma-1 receptor stimulation, thereby promoting mitochondrial ATP production.

[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

The Sigma-1 Receptor Ligands Chlorpromazine and Trifluoperazine Inhibit Na+ Transport in Frog Skin Epithelium

BIOPHYSICS ◽  
2020 ◽  
Vol 65 (5) ◽  
pp. 784-787
Author(s):  
A. V. Melnitskaya ◽  
Z. I. Krutetskaya ◽  
V. G. Antonov ◽  
N. I. Krutetskaya
Keyword(s):  
Frog Skin ◽  
Receptor Ligands ◽  
Na Transport ◽  
Sigma 1 Receptor ◽  
Skin Epithelium ◽  
Frog Skin Epithelium ◽  
Sigma 1

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.

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.

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