Distinct contribution of Rac1 expression in cardiomyocytes to anthracycline-induced cardiac injury

Henninger, Christian; Pohlmann, Stephanie; Ziegler, Verena; Ohlig, Jan; Schmitt, Joachim P.; Fritz, Gerhard

doi:10.1016/j.bcp.2019.03.038

Cited by 10 publications

(9 citation statements)

References 70 publications

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“…Dual-luciferase reporter gene assay showed that miR-93-5p could specifically bind to Rac1 (Figure 5B) (all p < 0.05). According to the previous literatures, overexpression of Rac1 can aggravate cardiomyocyte injury during myocardial I/R (27). Therefore, we speculated that circHIPK3 may absorb miR-93-5p, thus upregulating Rac1 expression and participating in myocardial injury after MI.…”

Section: Circhipk3 Sponges Mir-93-5p To Activate the Rac1/pi3k/akt Pathwaymentioning

confidence: 79%

“…Cardiac-specific deletion of Rac1 relieves I/R injury in diabetic hearts, whereas cardiomyocytes overexpressing Rac1 predisposes the heart to increased myocardial injury with enhanced contractile dysfunction (45). Knockout of Rac1 in cardiomyocytes partially protects against doxorubicin-induced cardiac injury (27). Rac1 participated in the pathological processes of different brain areas such as ischemic stroke, cognitive disorder, subarachnoid hemorrhage, and representative neuronal oxidative damage of several neurodegenerative disorders (44).…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

Yang

et al. 2021

Front. Cardiovasc. Med.

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The ceRNA network involving circular RNAs (circRNAs) is essential in the cardiovascular system. We investigated the underlying ceRNA network involving circHIPK3 in myocardial infarction (MI). After an MI model was established, cardiac function was verified, and myocardial tissue damage in mice with MI was evaluated. A hypoxia model of cardiomyocytes was used to simulate MI in vivo, and the expression of and targeting relationships among circHIPK3, miR-93-5p, and Rac1 were verified. The apoptosis of cardiomyocyte was identified. Gain- and loss-of-functions were performed to verify the ceRNA mechanism. The MI-modeled mice showed cardiac dysfunction and enlarged infarct size. CircHIPK3 was highly expressed in mouse and cell models of MI. Silencing circHIPK3 reduced infarct size, myocardial collagen deposition, and myocardial apoptosis rate and improved cardiac function. CircHIPK3 sponged miR-93-5p, and miR-93-5p targeted Rac1. Overexpression of miR-93-5p inhibited MI-induced cardiomyocyte injury and eliminated the harmful effect of circHIPK3. CircHIPK3 acted as ceRNA to absorb miR-93-5p, thus promoting the activation of the Rac1/PI3K/AKT pathway. We highlighted that silencing circHIPK3 can upregulate miR-93-5p and then inhibit the activation of Rac1/PI3K/Akt pathway, which can improve MI-induced cardiac dysfunction.

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Section: Circhipk3 Sponges Mir-93-5p To Activate the Rac1/pi3k/akt Pathwaymentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

Yang

et al. 2021

Front. Cardiovasc. Med.

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“…Rac1, a member of the small GTPase proteins, is the predominant isoform of Rac expressed in cardiomyocytes and is pivotal in cardiomyocyte apoptosis [10,11]. Previous studies demonstrated that Rac1 activation aggravates the damage of myocardial cells in the process of myocardial ischemiareperfusion through reactive oxygen species (ROS) generation by activating the NADPH oxidase [12].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Protects Cardiomyocytes from Oxygen Glucose Deprivation And Reperfusion-Induced Injury by Inhibiting Rac1/JNK/Foxo3a/Bim Signaling Pathway

Wang

Jin

Zhang

et al. 2021

Preprint

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Melatonin has been shown to exert protective effect during myocardial ischemia/reperfusion (I/R). However, the underlying mechanism is not completely understood. Using the oxygen-glucose deprivation and reperfusion (OGD/R) model of H9c2 cells in vitro, we found that melatonin alleviated OGD/R-induced H9c2 cell injury via inhibiting Foxo3a/Bim signaling pathway. Inhibition of Rac1 activation contributed to the protective effect of melatonin against OGD/R injury in H9c2 cells. Additionally, melatonin inhibited OGD/R-activated Foxo3a/Bim signaling pathway through inactivation of Rac1. Furthermore, JNK inactivation was responsible for Rac1 inhibition-mediated inactivation of Foxo3a/Bim signaling pathway and decreased cell injury in melatonin-treated H9c2 cells. Taken together, these findings identified a Rac1/JNK/Foxo3a/Bim signaling pathway in melatonin-induced protective effect against OGD/R injury in H9c2 cells. This study provided a novel insight into the protective mechanism of melatonin against myocardial I/R injury.

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“…Rac1, a member of the small GTPase proteins, is the predominant isoform of Rac expressed in cardiomyocytes and is pivotal in apoptosis of cardiomyocytes (Henninger et al, 2019; Su et al, 2019). Previous studies demonstrated that Rac1 activation aggravates the damage of cardiomyocytes in the process of myocardial I/R through reactive oxygen species (ROS) generation by activating the NADPH oxidase (Li et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin protects H9c2 cardiomyoblasts from oxygen‐glucose deprivation and reperfusion‐induced injury by inhibiting Rac1/JNK/Foxo3a/Bim signaling pathway

Wang

Jin

Zhang

et al. 2021

Cell Biology International

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Melatonin has been shown to protect against ischemia/reperfusion (I/R)‐induced myocardial injury, however, the precise molecular mechanisms have not been fully clarified. The present study was aimed to investigate whether inactivation of Rac1/JNK/Foxo3a/Bim signaling pathway is responsible for the protective effect of melatonin on I/R‐induced myocardial injury. Our results showed that Foxo3a downregulation contributed to the protective effect of melatonin on OGD/R‐induced injury of H9c2 cardiomyoblasts. Melatonin treatment led to a reduced activity of Rac1, which was responsible for Foxo3a downregulation and decreased cell injury in OGD/R‐exposed H9c2 cells. Furthermore, JNK acts as a downstream effector of Rac1 in mediating melatonin‐induced inactivation of Foxo3a/Bim signaling pathway and decreased cell injury in OGD/R‐exposed H9c2 cells. In conclusion, our results indicate that melatonin protects H9c2 cells against OGD/R‐induced injury by inactivating the Rac1/JNK/Foxo3a/Bim signaling pathway. This study provided a novel insight into the protective mechanism of melatonin against I/R‐induced myocardial injury.

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Distinct contribution of Rac1 expression in cardiomyocytes to anthracycline-induced cardiac injury

Cited by 10 publications

References 70 publications

RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

Melatonin Protects Cardiomyocytes from Oxygen Glucose Deprivation And Reperfusion-Induced Injury by Inhibiting Rac1/JNK/Foxo3a/Bim Signaling Pathway

Melatonin protects H9c2 cardiomyoblasts from oxygen‐glucose deprivation and reperfusion‐induced injury by inhibiting Rac1/JNK/Foxo3a/Bim signaling pathway

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