Knockdown of MicroRNA-122 Protects H9c2 Cardiomyocytes from Hypoxia-Induced Apoptosis and Promotes Autophagy

Zhang, Zaiwei; Li, Hu; Chen, Shasha; Li, Ying; Cui, Zhiyuan; Ma, Jie

doi:10.12659/msm.902936

Cited by 53 publications

(28 citation statements)

References 37 publications

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“…The live cells in normoxia were 91% and reduced to 61% in hypoxia, reaching a total of 67% cells injury. This is consistent with published works [25,29,30]. Transfection of MC did not induce any additional changes ( Figure 2b).…”

Section: The Protective Effect Of Let-7d-3p Is Mediated Via Apoptosissupporting

confidence: 93%

4927MicroRNA Let-7d-3p contributes to cardiac protection via targeting HMGA2

Wong

Saw

Lim

et al. 2018

European Heart Journal

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We tested the hypothesis that Let-7d-3p contributes to cardiac cell protection during hypoxic challenge. Myoblast H9c2 cells and primary neonatal rat ventricular cardiomyocytes (NRVM) were transfected with five selected miRNA mimics. Both cell lines were subjected to 0.2% oxygen hypoxia. The protective effects of these miRNAs were determined by assessment of cell metabolic activity by CCK8 assay and measurement of lactate dehydrogenase (LDH) release as a marker of cell injury. Apoptosis and autophagy flux were assessed by Annexin V/7-AAD double staining and the ratio of LC3 II/I with Baf-A1 treatment, an autophagy flux inhibitor, respectively. Luciferase-reporter assay, RT-qPCR and Western blots were performed to identify the changes of relevant gene targets. Among five miRNA mimic transfections, Let-7d-3p increased CCK8 activity, and decreased LDH release in both H9c2 and NRVM during hypoxia. Apoptosis was significantly reduced in H9c2 cells transfected with Let-7d-3p mimic. Autophagy and autophagy flux were not affected. In silico, mRNAs of HMGA2, YY1, KLF9, KLF12, and MEX3C are predicted targets for Let-7d-3p. Luciferase-reporter assay confirmed that Let-7d-3p bound directly to the 3'-UTR region of HMGA2, MEX3C, and YY1, the down-regulations of these mRNAs were verified in both H9c2 and NRVM. The protein expression of HMGA2, but not others, was downregulated in H9c2 and NRVM. It is known that HMGA2 is a strong apoptosis trigger through the blocking of DNA repair. Thus, we speculate that the anti-apoptotic effects of Let-7d-3p mimic during hypoxia challenge are due to direct targeting of HMGA2.

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Section: The Protective Effect Of Let-7d-3p Is Mediated Via Apoptosissupporting

confidence: 93%

4927MicroRNA Let-7d-3p contributes to cardiac protection via targeting HMGA2

Wong

Saw

Lim

et al. 2018

European Heart Journal

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“…Its occurrence is usually associated with acute continuous hypoxia-induced cardiomyocyte apoptosis and oxidative stress in coronary arteries [2]. In other words, hypoxia could promote myocardial cell apoptosis, induce reactive oxygen species (ROS) generation, and decrease the activity of antioxidant enzymes, including glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), aggravating the conditions of AMI [3,4]. Understanding the molecular mechanisms underlying hypoxia-induced apoptosis and oxidative stress in cardiomyocytes might help in the development of effective treatments for AMI.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Downregulation of miR-483-5p decreases hypoxia-induced injury in human cardiomyocytes by targeting MAPK3

Hao

Yuan

2020

Cell Mol Biol Lett

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Background: MiR-483-5p was recently identified as a risk factor in the early stages of acute myocardial infarction (AMI) patients. Here, we further investigated how miR-483-5p affects cardiomyocyte apoptosis and oxidative stress under hypoxic conditions. Methods: Plasma samples were collected from AMI patients and healthy volunteers. The expression of miR-483-5p was determined using quantitative real-time PCR. An in vitro hypoxic model was constructed to mimic AMI in AC16 cells. Cell viability, apoptosis and oxidative stress biomarker levels (MDA, SOD and CAT) were respectively determined using CCK-8, flow cytometry and commercial assay kits. Results: The expression levels of miR-483-5p were significantly higher in AMI patients than in control subjects. Circulating levels of miR-483-5p positively correlated with creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) levels. The in vitro experiments showed that the expression levels of miR-483-5p were also upregulated in hypoxia-induced AC16 cell injury. MiR-483-5p overexpression significantly increased hypoxia-induced cardiomyocyte apoptosis and oxidative stress, while knockdown attenuated these effects. Mechanistically, miR-483-5p directly targets MAPK3 in AC16 cells. Furthermore, the protective effects of miR-483-5p knockdown against hypoxiainduced cardiomyocyte injury are partially dependent on MAPK3. Conclusions: MiR-483-5p, which targets MAPK3, might be a potential therapeutic target for the diagnosis and prevention of hypoxia-induced myocardial injury.

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“…Acute ischemia leading to infarction is associated with a rapid sequence of pathologic changes that can result in irreversible cardiomyocytes damage, apoptosis, and necrosis [ 4 ], with subsequent segmental ventricular remodeling and expansion [ 5 ]. If the pathologic changes are not prevented, AMI may cause heart failure, arrhythmias, ventricular aneurysm formation, ventricular rupture, cardiogenic shock, and cardiac arrest [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis

et al. 2018

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Reperfusion after myocardial ischemia can induce cardiomyocyte death, known as myocardial reperfusion injury. The pathophysiology of the process of reperfusion suggests the confluence multiple pathways. Recent studies have focused on the inflammatory response, which is considered to be the main mechanism during the process of myocardial ischemia-reperfusion injury and can cause cardiomyocyte apoptosis. Peroxisome proliferator-activated receptors gamma activated by endogenous ligands and exogenous ligand can decrease the inflammatory response in cardiomyocytes. Thiazolidinediones are synthetic, high-affinity, selective ligands for peroxisome proliferator-activated receptors gamma, and can inhibit the inflammatory response, decrease myocardial infarct size, and protect cardiac function. However, thiazolidinediones, including rosiglitazone and pioglitazone, can also contribute to adverse cardiovascular events such as congestive heart failure. Therefore, there are some limitations to the use of thiazolidinediones. Most endogenous ligands were of low affinity until hexadecyl azelaoyl phosphatidylcholine was identified as a high-affinity ligand and agonist for peroxisome proliferator-activated receptors gamma. Hexadecyl azelaoyl phosphatidylcholine binds recombinant peroxisome proliferator-activated receptors with an affinity (Kd(app) ≈40 nM) which is equivalent to rosiglitazone. Therefore, hexadecyl azelaoyl phosphatidylcholine is a specific peroxisome proliferator-activated receptors gamma agonist. Given these findings, we hypothesized that the use of hexadecyl azelaoyl phosphatidylcholine can activate the peroxisome proliferator-activated receptors gamma signal pathways and prevent the inflammatory response process of myocardial ischemia-reperfusion injury, with reduced cardiomyocyte apoptosis and death.

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Knockdown of MicroRNA-122 Protects H9c2 Cardiomyocytes from Hypoxia-Induced Apoptosis and Promotes Autophagy

Cited by 53 publications

References 37 publications

4927MicroRNA Let-7d-3p contributes to cardiac protection via targeting HMGA2

4927MicroRNA Let-7d-3p contributes to cardiac protection via targeting HMGA2

RETRACTED ARTICLE: Downregulation of miR-483-5p decreases hypoxia-induced injury in human cardiomyocytes by targeting MAPK3

Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis

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