MicroRNA-223 protects neonatal rat cardiomyocytes and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1

Liu, Huan; Deng, Yunfei; Xu, Yu; Jin, Wei; Liu, Hongli

doi:10.1016/j.yjmcc.2018.03.018

Cited by 82 publications

(59 citation statements)

References 49 publications

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“…Mechanistically, PDK1 was found to be a direct target of miR-28 and target-binding assay using luciferase activity and PDK protein expression after transfection with miR-28 confirmed the prediction [ 190 ]. Similarly, miR-223 has been reported to play an important role in cell survival by regulation of autophagy and apoptosis [ 191 ]. The miR-223 was upregulated in the border zone of infarct area in rats subjected to LAD occlusion [ 191 ].…”

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

“…Similarly, miR-223 has been reported to play an important role in cell survival by regulation of autophagy and apoptosis [ 191 ]. The miR-223 was upregulated in the border zone of infarct area in rats subjected to LAD occlusion [ 191 ]. Moreover, overexpression of miR-223 protected H9c2 cells and neonatal rat cardiomyocytes (NRCMs) against hypoxia-induced apoptosis by directly targeting PARP-1 [ 191 ].…”

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

“…The miR-223 was upregulated in the border zone of infarct area in rats subjected to LAD occlusion [ 191 ]. Moreover, overexpression of miR-223 protected H9c2 cells and neonatal rat cardiomyocytes (NRCMs) against hypoxia-induced apoptosis by directly targeting PARP-1 [ 191 ]. Decisively, this study showed that H9c2 and NRCMs cells treated with miR-223 mimic increased p-AKT and p-mTOR expression under hypoxic conditions and the protective effect of miR-223 was abolished upon treatment with miR-223 inhibitor [ 191 ].…”

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

“…Moreover, overexpression of miR-223 protected H9c2 cells and neonatal rat cardiomyocytes (NRCMs) against hypoxia-induced apoptosis by directly targeting PARP-1 [ 191 ]. Decisively, this study showed that H9c2 and NRCMs cells treated with miR-223 mimic increased p-AKT and p-mTOR expression under hypoxic conditions and the protective effect of miR-223 was abolished upon treatment with miR-223 inhibitor [ 191 ]. Although, earlier study by van Rooij et al reported an upregulation of miR-223 in human failing heart tissues [ 192 ], but did not explore on the mechanism.…”

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

See 3 more Smart Citations

Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Samidurai

Kukreja

Das

2018

Oxidative Medicine and Cellular Longevity

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Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.

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Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Samidurai

Kukreja

Das

2018

Oxidative Medicine and Cellular Longevity

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“…In contrast to their adult state, mammalian neonatal cardiomyocytes allow the maintenance of a prolonged, physiologically contractive culture [36]. Murine neonatal cardiomyocytes have already been used to mimic diverse states of cardiac dysfunction, such as myocardial ischemia [37], ventricular hypertrophy [38], arrhythmia [39], and cellular senescence [40]. As studies on protein homeostasis (proteostasis) and contractility in cardiomyocyte aging remain a challenging task, culture of neonatal cardiomyocytes offers an optimal approach for manipulation studies under controlled conditions.…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

Häseli

Deubel

Jung

et al. 2020

Oxidative Medicine and Cellular Longevity

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Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated β-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.

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Troxerutin regulates HIF‐1α by activating JAK2/STAT3 signaling to inhibit oxidative stress, inflammation, and apoptosis of cardiomyocytes induced by H₂O₂

Li¹,

Yang

2021

Drug Development Research

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Heart failure (HF) is greatly threatening human health and affecting morbidity and mortality worldwide. Troxerutin can alleviate myocardial injury induced by ischemia and hypoxia. The present study aimed to investigate the protective effect of troxerutin on H2O2‐induced cardiomyocytes and the underlying molecular mechanism. Primary mouse cardiomyocytes morphology induced by H2O2 in a different duration time was observed by a microscope. After indicated treatment, the viability and apoptosis of cardiomyocytes were detected by CCK‐8 assay and flow cytometry analysis. The expression of inflammatory factors and oxidative stress biomarkers was detected by Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and assay kits. Hypoxia inducible factor‐1a (HIF‐1α) expression was determined by western blot analysis, RT‐qPCR analysis and immunofluorescence staining. The apoptosis‐related protein expression and the phosphorylation level of janus‐activated kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) were detected by the western blot analysis. As a result, after the H2O2 treatment in a different duration time, the primary mouse cardiomyocytes gradually stopped beating and the morphology of cardiomyocytes treated with H2O2 was changed significantly from fusiform shape to round shape. The viability of cardiomyocytes was decreased after H2O2 induction. The HIF‐1α expression was increased after the H2O2 treatment within 30 min while decreased over 30 min. In addition, troxerutin improved viability and suppressed apoptosis, inflammation and oxidative stress of H2O2‐induced cardiomyocytes, which was reversed by KC7F2 (a HIF‐1α inhibitor) or CHZ868 (a JAK inhibitor). To sum up, troxerutin could regulate HIF‐1α by activating JAK2/STAT3 signaling to inhibit oxidative stress, inflammation, and apoptosis of cardiomyocytes induced by H2O2.

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MicroRNA-223 protects neonatal rat cardiomyocytes and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1

Cited by 82 publications

References 49 publications

Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

Troxerutin regulates HIF‐1α by activating JAK2/STAT3 signaling to inhibit oxidative stress, inflammation, and apoptosis of cardiomyocytes induced by H₂O₂

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MicroRNA-223 protects neonatal rat cardiomyocytes and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1

Cited by 82 publications

References 49 publications

Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

Troxerutin regulates HIF‐1α by activating JAK2/STAT3 signaling to inhibit oxidative stress, inflammation, and apoptosis of cardiomyocytes induced by H2O2

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About

Troxerutin regulates HIF‐1α by activating JAK2/STAT3 signaling to inhibit oxidative stress, inflammation, and apoptosis of cardiomyocytes induced by H₂O₂