scholarly journals Overexpression of Long noncoding RNA Oprm1 Attenuates Myocardial Ischemia/Reperfusion Injury by Increasing Endogenous Hydrogen Sulfide Production via Oprm1/miR-30b-5p/CSE axis

2020 ◽  
Author(s):  
Xiaomin Hu ◽  
Bojiang Liu ◽  
Peng Wu ◽  
Yuheng Lang ◽  
Tong Li
Keyword(s):  
Myocardial Infarction ◽  
Hydrogen Sulfide ◽  
Cardiac Function ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Luciferase Reporter ◽  
H9c2 Cardiomyocytes

Abstract Background: Ischemia/Reperfusion (I/R) Injury largely limits the efficacy of revascularization in acute myocardial infarction. Long noncoding RNA (lncRNA) Oprm1 is protective in cerebral I/R injury. However, the effect of lncRNA Oprm1 on myocardial I/R injury and its mechanism remains unknown.Methods: We ligated and then released the left anterior descending coronary artery of adult male rats to build the I/R model in vivo, while an H9c2 cardiomyocytes hypoxia-reoxygenation (H/R) model was also used. Myocardial infarction area, cardiac function, histology, Tunnel staining, cell viability, and vital protein expression was conducted and compared.Results: lncRNA Oprm1 was significantly down-regulated in the I/R injury model. When administered with the AAV9-Oprm1 vector, the myocardial injury and cardiac function were mitigated and preserved, with apoptosis reduced. The cystathionine-γ-lyase (CSE) expression and hydrogen sulfide (H2S) expression were increased. The dual-luciferase reporter gene revealed the targeted relationship between lncRNA Oprm1 and miR-30b-5p. In H9c2 cardiomyocytes models, the miR-30b-5p blocked the protective effect of lncRNA Oprm1 on H/R injury, when Bcl-2, Bcl-xl was down-regulated, and HIF-1α, Bnip-3, Caspase-3, and Caspase-9 up-regulated.Conclusions: lncRNA Oprm1can competitively combines with miR-30b-5p, which down-regulates the expression of CSE. When administered with lncRNA Oprm1, increased endogenous H2S can reduce apoptosis and protect the myocardium from I/R injury via activating PI3K/Akt pathway and inhibiting HIF1-α activity.

scholarly journals Long noncoding RNA-MEG3 contributes to myocardial ischemia–reperfusion injury through suppression of miR-7-5p expression

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Liyuan Zou ◽  
Xiaokun Ma ◽  
Shuo Lin ◽  
Bingyuan Wu ◽  
Yang Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter

Abstract Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) plays an important role in protection of ischemia–reperfusion (I/R) injury in brain and liver. However, role of MEG3 in myocardial I/R injury remains unclear. Here, the role of MEG3 in protection of myocardial I/R injury and its association with microRNA-7-5p (miR-7-5p) was investigated using rat cardiac I/R model and myocardial I/R cell model. Our results showed that MEG3 was significantly up-regulated and miR-7-5p was significantly down-regulated after I/R. Following I/R, the levels of intact PARP and intact caspase-3 were reduced, while the cleaved fragments of PARP and caspase-3 were increased. TUNEL assay showed an increase in cardiomyocyte apoptosis after I/R. The levels of I/R-induced creatine kinase (CK) and lactate dehydrogenase (LDH) were inhibited by knockdown of MEG3 (siMEG3). SiMEG3 increased cell proliferation and inhibited cell apoptosis after I/R. In contrast, overexpression of MEG3 increased the I/R-induced CK and LDH activities and cell apoptosis and decreased cell proliferation. The dual-luciferase reporter system showed a direct binding of MEG3 to miR-7-5p. The level of miR-7-5p was negatively associated with the change in levels of MEG3 in H9c2 cells. The levels of intact RARP1 and caspase-3 were significantly increased by knockdown of MEG3. Co-transfection of miR-7-5p inhibitor with siMEG3 activates CK and LDH, significantly decreased cell proliferation, increased cell apoptosis, and decreased intact poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3. In summary, down-regulation of MEG3 protects myocardial cells against I/R-induced apoptosis through miR-7-5p/PARP1 pathway, which might provide a new therapeutic target for treatment of myocardial I/R injury.

scholarly journals The Cardioprotective Actions of Hydrogen Sulfide in Acute Myocardial Infarction and Heart Failure

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
David J. Polhemus ◽  
John W. Calvert ◽  
Javed Butler ◽  
David J. Lefer
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Multiple Organ ◽  
Organ Systems ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

It has now become universally accepted that hydrogen sulfide (H2S), previously considered only as a lethal toxin, has robust cytoprotective actions in multiple organ systems. The diverse signaling profile of H2S impacts multiple pathways to exert cytoprotective actions in a number of pathological states. This paper will review the recently described cardioprotective actions of hydrogen sulfide in both myocardial ischemia/reperfusion injury and congestive heart failure.

scholarly journals Downregulation of Long Noncoding RNA TUG1 Attenuate MTDH /NF-κB/IL-1β mediated inflammatory damage via Targeting miR-29b-1-5p After Spinal cord ischemia reperfusion in rats

2020 ◽  
Author(s):  
Hui Jia ◽  
Zhe Li ◽  
Bo Fang ◽  
Yi Chang ◽  
Yongjian Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Function ◽  
Noncoding Rna ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Spinal Cord Ischemia ◽  
Luciferase Reporter ◽  
Inflammatory Damage ◽  
Blood Spinal Cord Barrier

Abstract Background: Spinal cord ischemia reperfusion (IR) is associated with an inflammatory response. The long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) and microRNA-29b (miR-29b) family are frequently dysregulated in neuro-ischemic diseases. However, their potential roles in spinal cord IR injury (IR) are unknown. Methods: A spinal cord IR model was established in rats by14-minute occlusion of aortic arch. The aberrant miRNAs were identified by microarray analysis, and qRT-PCR was used to validate the lncRNA and microRNA levels. The motor function of the differentially-treated animals was assessed by Tarlov scores, and the leakage of Blood-spinal cord barrier (BSCB) was measured in terms of the extravasation of Evans blue (EB) dye. The expression levels of different proteins were analyzed by Western blotting and immunofluorescence. The interaction between TUG1 and miR-29b-1-5p, TRIL and miR-29b-1-5p, and MTDH and miR-29b-1-5p were determined using bioinformatics programs and the dual-luciferase reporter assay. Results: MiR-29b-1-5p was significantly downregulated and TUG1 was upregulated in the spinal cord of rats after IR. In addition, TRIL and MTDH protein levels were also significantly increased after IR. MTDH was predicted as a target of miR-29b-1-5p and its knockdown downregulated NF-κB and IL-1β levels. In addition, a direct interaction was observed between TUG1 and miR-29b-1-5p, and knocking down TUG1 upregulated the miRNA. Furthermore, overexpression of miR-29b-1-5p or TUG1 knockdown alleviated BSCB leakage and improved hind-limb motor function, and downregulated MTDH and its downstream pro-inflammatory cytokines. Suppression of miR-29b-1-5p reversed the neuroprotective effect of TUG1 knockdown, restored the levels of MTDH/ NF-κB/IL-1β and activated astrocytes. Conclusion: Downregulation of TUG1 alleviated MTDH/NF-κB/IL-1β pathway-mediated inflammatory damage after IR by targeting miR-29b-1-5p. Keywords: Spinal cord ischemia reperfusion injury, Neuroinflammation, Blood-spinal cord barrier, Astrocytes, TUG1, miR-29b-1-5p, MTDH

scholarly journals Silencing of Long Noncoding RNA AK139328 Attenuates Ischemia/Reperfusion Injury in Mouse Livers

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80817 ◽  
Author(s):  
Zhenzhen Chen ◽  
Shi Jia ◽  
Danhua Li ◽  
Junyan Cai ◽  
Jian Tu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

Hypertrophied myocardium is vulnerable to ischemia/reperfusion injury and refractory to rapamycin-induced protection due to increased oxidative/nitrative stress

2018 ◽  
Vol 132 (1) ◽  
pp. 93-110 ◽  
Author(s):  
Lei-Lei Ma ◽  
Yang Li ◽  
Pei-Pei Yin ◽  
Fei-Juan Kong ◽  
Jun-Jie Guo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiomyocyte Apoptosis ◽  
Coronary Artery Ligation ◽  
Nitrative Stress ◽  
Cardioprotective Effects

Left ventricular hypertrophy (LVH) is causally related to increased morbidity and mortality following acute myocardial infarction (AMI) via still unknown mechanisms. Although rapamycin exerts cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury in normal animals, whether rapamycin-elicited cardioprotection is altered in the presence of LVH has yet to be determined. Pressure overload induced cardiac hypertrophied mice and sham-operated controls were exposed to AMI by coronary artery ligation, and treated with vehicle or rapamycin 10 min before reperfusion. Rapamycin produced marked cardioprotection in normal control mice, whereas pressure overload induced cardiac hypertrophied mice manifested enhanced myocardial injury, and was refractory to rapamycin-elicited cardioprotection evidenced by augmented infarct size, aggravated cardiomyocyte apoptosis, and worsening cardiac function. Rapamycin alleviated MI/R injury via ERK-dependent antioxidative pathways in normal mice, whereas cardiac hypertrophied mice manifested markedly exacerbated oxidative/nitrative stress after MI/R evidenced by the increased iNOS/gp91phox expression, superoxide production, total NO metabolites, and nitrotyrosine content. Moreover, scavenging superoxide or peroxynitrite by selective gp91phox assembly inhibitor gp91ds-tat or ONOO− scavenger EUK134 markedly ameliorated MI/R injury, as shown by reduced myocardial oxidative/nitrative stress, alleviated myocardial infarction, hindered cardiomyocyte apoptosis, and improved cardiac function in aortic-banded mice. However, no additional cardioprotective effects were achieved when we combined rapamycin and gp91ds-tat or EUK134 in ischemic/reperfused hearts with or without LVH. These results suggest that cardiac hypertrophy attenuated rapamycin-induced cardioprotection by increasing oxidative/nitrative stress and scavenging superoxide/peroxynitrite protects the hypertrophied heart from MI/R.

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