Brain Sigma-1 Receptor Stimulation Improves Mental Disorder and Cardiac Function in Mice With Myocardial Infarction

2013 ◽  
Vol 62 (2) ◽  
pp. 222-228 ◽  
Author(s):  
Koji Ito ◽  
Yoshitaka Hirooka ◽  
Kenji Sunagawa
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Mental Disorder ◽  
Receptor Stimulation ◽  
Sigma 1 Receptor ◽  
Sigma 1

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

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

scholarly journals Stimulation of Sigma-1 Receptor Protects against Cardiac Fibrosis by Alleviating IRE1 Pathway and Autophagy Impairment

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Jing Qu ◽  
Miaoling Li ◽  
Dongxu Li ◽  
Yanguo Xin ◽  
Junli Li ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Er Stress ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Cardiac Fibroblast ◽  
Autophagic Flux ◽  
Sigma 1 Receptor ◽  
Fibroblast Activation ◽  
Sigma 1 ◽  
Stimulation Of

Sigma-1 receptor (Sig1R), a chaperone in the endoplasmic reticulum (ER) membrane, has been implicated in cardiac hypertrophy; however, its role in cardiac fibroblast activation has not been established. This study investigated the possible association between Sig1R and this activation by subjecting mice to sham, transverse aortic constriction (TAC), and TAC plus fluvoxamine (an agonist of Sig1R) treatments. Cardiac function and fibrosis were evaluated four weeks later by echocardiography and histological staining. In an in vitro study, neonatal rat cardiac fibroblasts were treated with fluvoxamine or NE-100 (an antagonist of Sig1R) in the presence or absence of transforming growth factor beta1 (TGF-β1). Fibrotic markers, ER stress pathways, and autophagy were then investigated by qPCR, western blotting, immunofluorescence, confocal microscopy, and transmission electron microscopy. Fluvoxamine treatment reduced cardiac fibrosis, preserved cardiac function, and attenuated cardiac fibroblast activation. Inhibition of the IRE1/XBP1 pathway, a branch of ER stress, by a specific inhibitor of IRE1 endonuclease activity, attenuated the pathological process. Fluvoxamine stimulation of Sig1R restored autophagic flux in cardiac fibroblasts, indicating that Sig1R appears to play a protective role in the activation of cardiac fibroblasts by inhibiting the IRE1 pathway and restoring autophagic flux. Sig1R may therefore represent a therapeutic target for cardiac fibrosis.

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.

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