MiR-219a-2 relieves myocardial ischemia-reperfusion injury by reducing calcium overload and cell apoptosis through HIF1α/ NMDAR pathway

Hu, Fudong; Zhang, Shengye; Chen, Xi; Fu, Xin; Guo, Shengcun; Jiang, Zhengming; Chen, Kui

doi:10.1016/j.yexcr.2020.112172

Cited by 21 publications

(10 citation statements)

References 21 publications

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“…Increased activity of IP3Rs causes mitochondrial Ca 2+ overload which can lead to apoptosis 9 . During the process of MI/R injury, the [Ca 2+ ]i concentration continues to increase and leads to cardiomyocyte apoptosis and myocardial damage 37 . After downregulating IP3R1 expression in myocardial tissue of MI/R rats using shRNA, the Ca 2+ level in mitochondria was clearly decreased; similar results were found in H/R-challenged cells.…”

Section: Discussionmentioning

confidence: 99%

IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

Liu

Zhong

et al. 2021

Cell Death Discov.

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Intracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.

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Section: Discussionmentioning

confidence: 99%

IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

Liu

Zhong

et al. 2021

Cell Death Discov.

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“…We will further investigate other genes that may be implicated in the mechanism of TGP in H/R-induced cardiomyocyte pyroptosis, and conduct animal experiments to verify our cell experiment results. In addition, MI/RI can cause calcium overload, and reducing calcium overload can also alleviate MI/ RI injury to a certain extent (He et al 2018;Hu et al 2020;. It has been reported that ADCY1 can affect the release of Ca 2+ (Jackson et al 2011;Kitaguchi et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of total glucosides of paeony in hypoxia/reoxygenation-induced cardiomyocyte pyroptosis

Yan

Huang

2021

J Bioenerg Biomembr

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Inflammasome-mediated pyroptosis can aggravate myocardial ischemia/reperfusion injury. Total glucosides of paeony (TGP) is widely used in anti-inflammation. This study investigated the effect of TGP on pyroptosis of hypoxia/reoxygenation (H/R)induced cardiomyocytes. HL-1 cells were subjected to H/R treatment. H/R-induced cardiomyocytes were treated with TGP at different concentrations (50, 100, and 200 mg/kg). The viability of H/R-induced cardiomyocytes was measured. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were determined. The activity of caspase-1, the expressions of NLRP3 and GSDMD-N, and the concentrations of IL-1β and IL-18 were examined. miR-181a-5p expression in H/R cardiomyocytes was determined. The targeting relationship between miR-181a-5p and adenylate cyclase 1 (ADCY1) was verified. Functional rescue experiments were performed to verify the effect of miR-181a-5p or ADCY1 on the pyroptosis of H/R cardiomyocytes. TGP enhanced H/R-induced cardiomyocyte viability in a dose-dependent manner, reduced LDH, MDA, and ROS levels, increased SOD level, decreased caspase-1 activity, reduced NLRP3 and GSDMD-N expressions, and inhibited IL-1β and IL-18 concentrations. TGP suppressed miR-181a-5p expression in H/R cardiomyocytes. miR-181a-5p targeted ADCY1. miR-181a-5p overexpression or ADCY1 inhibition reversed the inhibitory effect of TGP on the pyroptosis of H/R cardiomyocytes. Collectively, TGP alleviated the pyroptosis of H/R cardiomyocytes via the miR-181a-5p/ADCY1 axis.

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“…MicroRNA-219-5p alleviates morphine tolerance by inhibiting the CaMKII/NMDAR pathway (Wang J. et al, 2017). Meanwhile, microRNA-219a-2 has been reported to reduce calcium overload and apoptosis through HIF1α/NMDAR pathway, thus alleviating myocardial ischemia-reperfusion injury (Hu et al, 2020). MicroRNA-182-5p regulates nerve injury-induced nociceptive hypersensitivity by targeting Ephrin type-b receptor 1 (EphB1) which interacts with the NMDAR (Zhou et al, 2017).…”

Section: Microrna and Nmdarmentioning

confidence: 99%

Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

Chen

Liu

et al. 2022

Front. Mol. Neurosci.

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Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.

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MiR-219a-2 relieves myocardial ischemia-reperfusion injury by reducing calcium overload and cell apoptosis through HIF1α/ NMDAR pathway

Cited by 21 publications

References 21 publications

IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

Mechanism of total glucosides of paeony in hypoxia/reoxygenation-induced cardiomyocyte pyroptosis

Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

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