Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy

Zhu, Han-Hua; Wang, Xiantao; Sun, Yani; He, Wei; Liang, Jing; Mo, Bing-hai; Li, Lang

doi:10.1159/000493817

Cited by 29 publications

(18 citation statements)

References 39 publications

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“…After percutaneous coronary intervention, 57% of patients with ST-segment elevation myocardial infarction develop microvascular obstruction [15], which could lead to persistent hypoxia in cardiac microcirculation, loss of cardiomyocytes and adverse ventricular remodeling [16]. In in vitro model, H/R has been wildly used in generating myocardial ischemia/reperfusion-induced injury [17].…”

Section: Discussionmentioning

confidence: 99%

Withdrawn: MicroRNA‐142‐5p inhibits autophagy in cardiomyocytes in a mouse model of hypoxia/reoxygenation

2021

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Cardiomyocyte hypoxia-and ischemia-induced apoptosis is a key challenge in the treatment of cardiovascular diseases, and it has been previously reported that high glucose-induced cardiomyocyte apoptosis can be prevented by autophagy activation. Furthermore, down-regulation of the microRNA miR-142-5p protects cardiomyocytes against hypoxia. However, the effects of miR-142-5p on autophagy of myocardial cells under hypoxia/reoxygenation (H/R) are less well understood. Here, we observed that the optimal time for hypoxia and re-oxygenation was 4 hours (h) and 8 h in our model. Overexpression of miR-142-5p in a cardiomyocyte model of H/R enhanced apoptosis and increased the expression of interleukin-1β (IL-1β), cleaved-caspase 3 and p62, but inhibited autophagy and decreased expression of Beclin-1, protein 1 light chain 3B (LC3B) and B cell leukemia/lymphoma 2 (Bcl-2) at the mRNA and protein level. Silencing of miR-142-5p had the opposite effects. We identified Beclin-1 as a target gene for miR-142-5p. Down-regulation of Beclin-1 inhibited autophagy, with down-regulation of LC3B and up-regulation of p62, but promoted apoptosis in the H/R model; down-regulation of miR-142-5p promoted autophagy and inhibited apoptosis in cardiomyocytes through up-regulation of BECN1. Our results provide new insights that may facilitate the development of treatments for ischemic heart disease.

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Section: Discussionmentioning

confidence: 99%

Withdrawn: MicroRNA‐142‐5p inhibits autophagy in cardiomyocytes in a mouse model of hypoxia/reoxygenation

2021

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“…Culture media were changed after 36 hours. To replicate an ischemic environment, the culture media were replaced with FBS-free low-glucose DMEM media (Gibco, USA) and then incubated in a hypoxia incubator (HERAcell VIOS 160i, Thermo Scientific, Waltham, MA, USA) at 37°C, saturated with 3% oxygen, 5% carbon dioxide, and 92% nitrogen, as previously described [21].…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

Wang

Sun

et al. 2020

BioMed Research International

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Background. Microvascular obstruction (MVO) can result in coronary microcirculation embolism and myocardial microinfarction. Myocardial injury induced by MVO is characterized by continuous ischemia and hypoxia of cardiomyocytes. Autophagy and apoptosis are closely associated with various cardiovascular diseases. Based on our previous study, we observed a decrease in miR-30e-3p expression and an increase in Egr-1 expression in a rat coronary microembolization model. However, the specific function of miR-30e-3p in regulating autophagy and apoptosis in an ischemia/hypoxia (IH) environment remains to be deciphered. We exposed cardiomyocytes to an IH environment and then determined whether miR-30e-3p was involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by regulating Egr-1. Methods. Cardiomyocytes were isolated from rats for our in vitro study. miR-30e-3p was either overexpressed or inhibited by transfection with lentiviral vectors into cardiomyocytes. 3-Methyladenine (3-MA) was used to inhibit autophagy. RT-qPCR and western blotting were used to determine the expression levels of miR-30e-3p, Egr-1, and proteins related to the autophagy and apoptosis process. Autophagic vacuoles and autophagic flux were evaluated using transmission electron microscopy (TEM) and confocal microscopy, respectively. Cardiomyocyte viability was evaluated using the MTS assay. Cell injury was assessed by lactate dehydrogenase (LDH) leakage, and apoptosis was determined by flow cytometry. Results. Both miR-30e-3p expression and autophagy were significantly inhibited, and apoptosis was increased in cardiomyocytes after 9 hours of IH exposure. Overexpression of miR-30e-3p increased autophagy and inhibited apoptosis, as well as suppressed Egr-1 expression and decreased cell injury. In addition, inhibition of miR-30e-3p reduced autophagy and increased apoptosis and cell injury. Conclusions. miR-30e-3p may be involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by indirectly regulating Egr-1 expression in an IH environment.

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“…Autophagy, an evolutionarily conserved form of "self-digestion", plays dual roles in the heart [10]. Recent studies on autophagy have shown both the protective [11] and deleterious [12] effects of autophagy in cardiomyocytes against oxidative stress. Evidence has revealed a strong correlation between modulation of NF-κB and the autophagic response [13,14].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation

et al. 2020

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Background: Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H 2 O 2) by inhibiting the NF-κB pathway. Methods: The IκBα S32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H 2 O 2 treatment. NRVMs were divided into control, H 2 O 2 , GFP + H 2 O 2 , IκBα+H 2 O 2 , and pyrrolidine dithiocarbamate (PDTC) + H 2 O 2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H 2 O 2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis-and autophagy-related proteins. Results: IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H 2 O 2. Meanwhile, IκBα overexpression decreased H 2 O 2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H 2 O 2 stimulation.

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Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy

Cited by 29 publications

References 39 publications

Withdrawn: MicroRNA‐142‐5p inhibits autophagy in cardiomyocytes in a mouse model of hypoxia/reoxygenation

Withdrawn: MicroRNA‐142‐5p inhibits autophagy in cardiomyocytes in a mouse model of hypoxia/reoxygenation

miR-30e-3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr-1 during Ischemia/Hypoxia

Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation

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