GPER agonist G1 suppresses neuronal apoptosis mediated by endoplasmic reticulum stress after cerebral ischemia/reperfusion injury

Han, Zhaobin; Chang, Yue-Chen; Zhou, Ying; Zhang, Hang; Chen, Long; Zhang, Yang; Si, Jun‐Qiang; Li, Li

doi:10.4103/1673-5374.251571

Cited by 23 publications

(12 citation statements)

References 54 publications

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“…When ERS occurs, heat shock protein family A (Hsp70) member 5 (GRP78) is isolated from these signal receptor molecules, which assists in the process of enabling unfolded or misfolded proteins to recover their correct conformation, and activating these signal receptor molecules, affecting the downstream CHOP levels ( 22 ). Previous studies have shown that the inhibition of ERS-mediated apoptosis leads to a decrease in CIRI-induced injury ( 12 , 23 , 24 ). Therefore, the ER should serve an important role in the development of CIRI.…”

Section: Discussionmentioning

confidence: 97%

Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis

Gao

et al. 2021

Exp Ther Med

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The endoplasmic reticulum stress (ERS) response serves an important role in cerebral ischemia-reperfusion injury (CIRI). However, to the best of the our knowledge, the effect of rosuvastatin on the ERS response in CIRI has not yet been studied. In the present study, the effect of rosuvastatin on cell damage in CIRI was investigated; furthermore, the effect of rosuvastatin on the ERS response was explored. Firstly, a hypoxia/reoxygenation (H/R)-induced cell damage model was established in PC12 cells. Cell viability was subsequently detected by a Cell Counting Kit-8 assay. A lactate dehydrogenase kit was used to detect cytotoxicity. TUNEL assay was then used to measure the extent of cell apoptosis, and western blotting was used to analyze the expression levels of the apoptosis-associated proteins Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9. In addition, western blotting was used to detect the expression levels of ERS-associated proteins, including phosphorylated (p)-protein kinase R-like endoplasmic reticulum kinase (PERK), p-eukaryotic initiation factor 2α and other proteins. Treatment with rosuvastatin led to an increased activity of H/R-induced PC12 cells and a decrease in their cytotoxicity. Rosuvastatin also led to an inhibition in apoptosis and ERS in H/R-induced PC12 cells. After administration of the ERS response activator thapsigargin (TG), TG was found to reverse the protective effect of rosuvastatin on injury of H/R-induced PC12 cells. Taken together, these findings have shown that rosuvastatin is able to protect PC12 cells from H/R-induced injury via inhibiting ERS-induced apoptosis, providing a strong theoretical basis for the use of rosuvastatin in the clinical treatment of CIRI.

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Section: Discussionmentioning

confidence: 97%

Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis

Gao

et al. 2021

Exp Ther Med

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“…Recently, there has been increasing evidence that neuronal apoptosis is also a key reason for CNS dysfunction after I/R [ 5 , 34 ]. Apoptotic programmed cell death is mainly induced by specific proteins such as Apaf-1, as well as proteins in the Bcl-2 and caspase families [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine post-conditioning attenuates cerebral ischemia following asphyxia cardiac arrest through down-regulation of apoptosis and neuroinflammation in rats

LeiQian

et al. 2021

BMC Anesthesiol

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Background Neuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research. This study was designed to investigate the neuroprotective effects of dexmedetomidine following resuscitation and potential mechanisms. Methods Anesthetized rats underwent 6-min asphyxia-based cardiac arrest and resuscitation, after which the experimental group received a single intravenous dose of dexmedetomidine (25 μg/kg). Neurological outcomes and ataxia were assessed after the return of spontaneous circulation. The serum levels and brain expression of inflammation markers was examined, and apoptotic cells were quantified by TUNEL staining. Results Neuroprotection was enhanced by dexmedetomidine post-conditioning after the return of spontaneous circulation. This enhancement was characterized by the promotion of neurological function scores and coordination. In addition, dexmedetomidine post-conditioning attenuated the serum levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α at 2 h, as well as interleukin IL-1β at 2, 24, and 48 h. TUNEL staining showed that the number of apoptotic cells in the dexmedetomidine post-conditioning group was significantly reduced compared with the control group. Further western blot analysis indicated that dexmedetomidine markedly reduced the levels of caspase-3 and nuclear factor-kappa B (NF-κB) in the brain. Conclusions Dexmedetomidine post-conditioning had a neuroprotective effect against cerebral injury following asphyxia-induced cardiac arrest. The mechanism was associated with the downregulation of apoptosis and neuroinflammation.

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“… Li et al (2016) provided evidence that GPER1 inhibits colonic motility by enhancing nitric oxide release from nitrergic nerves. GPER1 also appears to exert an inhibitory effect on neuronal apoptosis in the hippocampus ( Han et al, 2019 ). Furthermore, GPER1 activation induces bradycardic effects via activation of cardiac parasympathetic neurons ( Brailoiu et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Functional Interaction of Endothelin Receptors in Mediating Natriuresis Evoked by G Protein–Coupled Estrogen Receptor 1

Gohar

Pollock

2020

J Pharmacol Exp Ther

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The G protein–coupled estrogen receptor 1 (GPER1) mediates rapid estrogenic signaling. We recently reported that activation of GPER1 in the renal medulla evokes endothelin-1–dependent natriuresis in female, but not male, rats. However, the involvement of the ET receptors, ET A and ET B , underlying GPER1 natriuretic action remain unclear. In this study, we used genetic and pharmacologic methods to identify the contributions of ET A and ET B in mediating this female-specific natriuretic effect of renal medullary GPER1. Infusion of the GPER1-selective agonist G1 (5 pmol/kg per minute) into the renal medulla for 40 minutes increased Na + excretion and urine flow in anesthetized female ET B -deficient (ET B def) rats and littermate controls but did not affect blood pressure or urinary K + excretion in either group. Pretreatment with the selective ET A inhibitor ABT-627 (5 mg/kg, intravenous) abolished G1-induced natriuresis in ET B def rats. To further isolate the effects of inhibiting either receptor alone, we conducted the same experiments in anesthetized female Sprague-Dawley (SD) rats pretreated or not with ABT-627 and/or the selective ET B inhibitor A-192621 (10 mg/kg, intravenous). Neither antagonism of ET A nor antagonism of ET B receptor alone affected the G1-induced increase in Na + excretion and urine flow in SD rats. However, simultaneous antagonism of both receptors completely abolished these effects. These data suggest that ET A and ET B receptors can mediate the natriuretic and diuretic response to renal medullary GPER1 activation in female rats. SIGNIFICANCE STATEMENT Activation of G protein–coupled estrogen receptor 1 (GPER1) in the renal medulla of female rats evokes natriuresis via endothelin receptors A and/or B, suggesting that GPER1 and endothelin signaling pathways help efficient sodium excretion in females. Thus, GPER1 activation could be potentially useful to mitigate salt sensitivity in females.

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GPER agonist G1 suppresses neuronal apoptosis mediated by endoplasmic reticulum stress after cerebral ischemia/reperfusion injury

Cited by 23 publications

References 54 publications

Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis

Rosuvastatin protects PC12 cells from hypoxia/reoxygenation‑induced injury by inhibiting endoplasmic reticulum stress‑induced apoptosis

Dexmedetomidine post-conditioning attenuates cerebral ischemia following asphyxia cardiac arrest through down-regulation of apoptosis and neuroinflammation in rats

Functional Interaction of Endothelin Receptors in Mediating Natriuresis Evoked by G Protein–Coupled Estrogen Receptor 1

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