Involvement of cardiomyocyte apoptosis in myocardial injury of hereditary epileptic rats

Chen, Fan; Cao, Yonggang; Qi, Hanping; Li, Lei; Huang, Wei; Wang, Ye; Sun, Hai‐Ying

doi:10.1139/cjpp-2013-0005

Cited by 5 publications

(7 citation statements)

References 42 publications

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“…Our results indicated that the protein expression of CaSR was upregulated in TRM rat hearts, and this change strongly suggested that CaSR might be involved in epilepsy-induced cardiac injury. We previously found remarkable cardiac dysfunction and cardiomyocyte apoptosis in TRM rat hearts [14]. In this study, we also observed cardiac collagen deposits in TRM rat hearts.…”

Section: Discussionsupporting

confidence: 69%

“…Total proteins of the left ventricle myocardium were prepared and quantified using the BCA protein assay reagent, and the expression of specific proteins was analyzed through Western blot analysis as previously described by Chen et al [14]. Primary antibodies were as follows: CaSR (1:2,000), caspase-3 (1:200), Bcl-2 (1:200), Bax (1:200), ERK1/2 (1:200), JNK (1:200), p38 (1:200), TGF-β 1 (1:400), CTGF (1:2,000), collagen I (1:2,000), collagen III (1:2,000), and GAPDH (1:5,000).…”

Section: Methodsmentioning

confidence: 99%

“…The mechanisms of apoptosis might be associated with the activation of the mitochondria-initiated and the mitogen-activated protein kinase (MAPK) pathways [14]. We have recently found that the CaSR protein level was increased in the TRM rat.…”

Section: Introductionmentioning

confidence: 99%

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Role of Calcium-Sensing Receptor in Cardiac Injury of Hereditary Epileptic Rats

Chen

Cao

et al. 2015

Pharmacology

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Background: It has been reported that epilepsy leads to cardiac injury, but the underlying mechanisms have not yet been elucidated. Studies indicated that the calcium-sensing receptor (CaSR) is involved in cardiomyocyte apoptosis. However, the role of CaSR in epilepsy-induced cardiac injury remains unclear. Objective: The aim of this study was to investigate the effects of CaSR on cardiac injury of hereditary epileptic rats. Methods: The tremor (TRM) rat was used as an epilepsy model. Apoptotic rate, collagen volume fraction, and the expression of CaSR, Bcl-2, Bax, caspase-3, extracellular signal-regulated protein kinase (ERK), c-Jun NH₂-terminal protein kinase (JNK), p38 mitogen-activated protein kinase (MAPK), transforming growth factor-β₁ (TGF-β₁), connective tissue growth factor (CTGF), collagen I and collagen III protein were analyzed. Results: The results showed that the CaSR protein was increased in TRM rat hearts. Cardiac apoptosis and fibrosis were also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Masson's trichrome staining, respectively. Further results demonstrated that the expression of Bax, caspase-3, P-JNK, P-p38, TGF-β₁, CTGF, collagen I and collagen III protein were upregulated, whereas Bcl-2 and P-ERK were downregulated in TRM rat hearts. Moreover, these deleterious changes were further aggravated by GdCl₃ and attenuated by NPS-2390. Conclusions: Our results suggest that CaSR promotes cardiac apoptosis and fibrosis in TRM rat through the induction of mitochondrial and MAPK pathways as well as the activation of TGF-β₁ and CTGF.

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Section: Discussionsupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

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Role of Calcium-Sensing Receptor in Cardiac Injury of Hereditary Epileptic Rats

Chen

Cao

et al. 2015

Pharmacology

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“…Thus, cardiomyocyte apoptosis may be associated with activation of the mitogenactivated protein kinase pathway and mitochondria-initiated intrinsic pathway. 30 While many studies have focused on noting changes in electrocardiogram measurements, blood pressure, and myocar- dial histopathology, the underlying molecular mechanisms and involved biological pathways associated with cardiac injury in epilepsy remain elusive. In this study, we used iTRAQ-based proteomics to examine rat myocardial tissue and to explore molecular proteomic differences to reveal physiological/ pathological mechanisms leading to cardiac injury after recurrent seizures.…”

Section: ■ Discussionmentioning

confidence: 99%

Quantitative Proteomic Analysis To Identify Differentially Expressed Proteins in Myocardium of Epilepsy Using iTRAQ Coupled with Nano-LC–MS/MS

Zhang¹,

Zhang²,

et al. 2017

J. Proteome Res.

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Epilepsy is a difficult-to-manage neurological disease that can result in organ damage, such as cardiac injury, that contributes to sudden unexpected death in epilepsy (SUDEP). Although recurrent seizure-induced cardiac dysregulation has been reported, the underlying molecular mechanisms are unclear. We established an epileptic model with Sprague-Dawley rats by applying isobaric tags for a relative and absolute quantification (iTRAQ)-based proteomics approach to identify differentially expressed proteins in myocardial tissue. A total of seven proteins in the acute epilepsy group and 60 proteins in the chronic epilepsy group were identified as differentially expressed. Bioinformatics analysis suggested that the pathogenesis of cardiac injury in acute and chronic epilepsy may be due to different molecular mechanisms. Three proteins, a receptor for activated protein kinase C1 (RACK1), aldehyde dehydrogenase 6 family member A1 (ALDH6A1), and glycerol uptake/transporter 1 (Hhatl), were identified as playing crucial roles in cardiac injury during epilepsy and were successfully confirmed by Western blot and immunohistochemistry analysis. Our study not only provides a deeper understanding of the pathophysiological mechanisms of myocardial damage in epilepsy, but also suggests some potential novel therapeutic targets for preventing cardiac injury and reducing the incidence of sudden death due to heart failure.

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“…The downregulation of ASK1 expression may reduce apoptosis and the myocardial infarct size in a rat model of ischemia/reperfusion [ 35 ]. Moreover, it has been reported that cardiomyocyte apoptosis is involved in the myocardial injury of tremor rats by reducing Bcl-2 and p-ERK1/2, upregulating Bax, p-JNK, and p-p38, and activating caspase-3 [ 36 ]. In this study, we determined that miR-320 regulates the expression of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ASK1, p-JNK and p-p38 in cardiomyocytes after H/R injury by targeting AKIP1.…”

Section: Discussionmentioning

confidence: 99%

MiR-320 regulates cardiomyocyte apoptosis induced by ischemia–reperfusion injury by targeting AKIP1

Tian

Jiang

2018

Cell Mol Biol Lett

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BackgroundMicroRNAs play important roles in regulation of the cardiovascular system. The purpose of this study was to investigate microRNA-320 (miR-320) expression in myocardial ischemia-reperfusion (I/R) injury and the roles of miR-320 in cardiomyocyte apoptosis by targeting AKIP1 (A kinase interacting protein 1).MethodsThe level of miR-320 was detected using quantitative real-time polymerase chain reaction (qRT-PCR), and cardiomyocyte apoptosis was detected via terminal dUTP nick end-labeling assay. Cardiomyocyte apoptosis and the mitochondrial membrane potential were evaluated via flow cytometry. Bioinformatics tools were used to identify the target gene of miR-320. The expression levels of AKIP1 mRNA and protein were detected via qRT-PCR and Western blot, respectively.ResultsBoth the level of miR-320 and the rate of cardiomyocyte apoptosis were substantially higher in the I/R group and H9c2 cells subjected to H/R than in the corresponding controls. Overexpression of miR-320 significantly promoted cardiomyocyte apoptosis and increased the loss of the mitochondrial membrane potential, whereas downregulation of miR-320 had an opposite effect. Luciferase reporter assay showed that miR-320 directly targets AKIP1. Moreover, knock down and overexpression of AKIP1 had similar effects on the H9c2 cells subjected to H/R.ConclusionsmiR-320 plays an important role in regulating cardiomyocyte apoptosis induced by I/R injury by targeting AKIP1 and inducing the mitochondrial apoptotic pathway.Electronic supplementary materialThe online version of this article (10.1186/s11658-018-0105-1) contains supplementary material, which is available to authorized users.

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Involvement of cardiomyocyte apoptosis in myocardial injury of hereditary epileptic rats

Cited by 5 publications

References 42 publications

Role of Calcium-Sensing Receptor in Cardiac Injury of Hereditary Epileptic Rats

Role of Calcium-Sensing Receptor in Cardiac Injury of Hereditary Epileptic Rats

Quantitative Proteomic Analysis To Identify Differentially Expressed Proteins in Myocardium of Epilepsy Using iTRAQ Coupled with Nano-LC–MS/MS

MiR-320 regulates cardiomyocyte apoptosis induced by ischemia–reperfusion injury by targeting AKIP1

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