International Journal of Clinical and Experimental Pathology
·
2015
·
IF 1.891
Jing Zhao,Li Li,Ling Peng
The previous studies identify mammalian heart is terminal differentiation organs without regenerative capacity. Recently, there is some evidence point that cardiomyocytes are not terminally differentiated cells and cell proliferation may be stimulated in the pathologic heart. The aim of this study is to discover the possible mechanism which involved in cardiomyocytes proliferation process. In this study, the proliferation assay and cell cycle assay showed the proliferation of cardiomyocytes was inhibited when the cells treated with MAPK1 inhibitor. Moreover, the bioinformatics analysis revealed MAPK1 was positively correlated with MALAT1. Meanwhile, the expression of MALAT1 in H9C2 cells with the treatment of MAPK1 siRNA was obvious lower than scramble siRNA treated group. Finally further study suggested H9C2 cells treated with Wortmannin in combination with LY294002 (PI3K/AKT signaling pathway inhibitor), the expression of MALAT1 was dramatically decreased. These results indicated that MAPK1 was able to increase the proliferation of cardiomyocytes via up-regulating the expression of MALAT1 through PI3K/AKT signaling pathway.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-14
·
IF 3.8
Zheng Zihan,Liu YiZhen,Chen Danli,Yang Jianjun,Ren Lingxuan,Jin Zhen,Wang Weirong,Liu Xuyang,He Jianyu,Zheng Nanbo,Lin Rong
Background and purpose: Catalpol (CAT) has diverse pharmacological functions, including cellular homeostasis maintenance and anti-inflammatory effects. Sirtuin 5 (SIRT5) plays a considerable role in regulating cellular homeostasis in cardiac diseases. Our research explores the therapeutic potential of CAT against myocardial injury and its underlying mechanism. Methods: The H9c2 cells were pretreated with different CAT concentrations for 24 h, or CAT for 24 h followed by CoCl 2 stimulation. Cell viability was determined with MTT assay. Biochemical assays, western blotting, and quantitative real-time PCR (qRT-PCR), combined with bioinformatic analysis, were used to examine the impact of CAT on CoCl 2 -induced myocardial injury in H9c2 cells and further explore its molecular mechanisms. Results: CAT ameliorated levels of myocardial enzymes, increased nicotinamide adenine dinucleotide (NAD + /NADH) ratio and adenosine triphosphate (ATP), while inhibited lactic acid (LD), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 in CoCl 2 -induced H9c2 cells. Mechanistically, SIRT5 knockdown inhibited Lin28a expression and negated the effects of CAT on ATP level, LD content, and the expression of inflammatory factors in cells. CAT likely exerted its protective effects on myocardial function through the SIRT5-mediated signaling pathway. Conclusions: CAT regulates energy metabolism and inflammation via the SIRT5-mediated signaling pathway, exerting a protective effect in myocardial injury.
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
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IF 3.457
Min Chen,Xiaodong Wang,Bo Hu,Jian Zhou,Xin Wang,Wei Wei,Hua Zhou
Echinacoside is a natural ingredient with various pharmacological activities . In this study, we investigated the protective effects of echinacoside on cardiomyocytes (rat H9c2 cells) in an anoxia/reperfusion (A/R) model. Further, the regulatory function of sodium-calcium exchanger protein 3 (SLC8A3/NCX3) as well as the protein kinase B (AKT) signaling were studied. The present results indicated that echinacoside protected against A/R-induced apoptosis in a dose manner, which was characterized by a decrease in the apoptosis and caspase 3 protein levels in H9c2 cells. Further, Ca 2+ uptake were dose-dependently reduced in H9c2 cells by echinacoside under A/R conditions. Whereas, relative mRNA expression of SLC8A3 and protein levels of SLC8A3 and p-AKT showed opposite tendency. On the one hand, the A/R-induced abnormalities in H9c2 cells were remarkably ameliorated by activated p-AKT and over-expression of SLC8A3 but aggravated by inhibited p-AKT, and the aggravated effection were ameliorated by echinacoside. Moreover, protein levels of SLC8A3 were positively regulated by p-AKT signaling. On the other hand, apoptosis and Ca 2+ uptake as well as protein levels of caspase 3 were significantly increased by SLC8A3 silencing in H9c2 cells under normoxic conditions, and this symptom was remarkably reversed by echinacoside or Nimodipine (an antagonis of Ca 2+ ) treatment . Collectively, echinacoside has showed a cardioprotective effect against A/R treatment in a dose dependent manner in vitro, and this cardioprotective effect was potentially achieved via up-regulating p-AKT and SLC8A3.
研究领域:
药理学
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心脏病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 43
·期 2
·626-635
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IF 5.104
Zhang Yan-Yan,Yi Minhan,Huang Yong-Pan
Background/Aims: Doxorubicin-induced cardiac toxicity has been a major concern of oncologists and is considered the main restriction on its clinical application. Oxymatrine has shown potent anti-cancer, anti-fibrosis, and anti-oxidative effects. Recently, it has been reported that oxymatrine is protective against some cardiovascular diseases. In this study, we aimed to investigate the effects of oxymatrine on doxorubicin-induced cardiotoxicity in rat hearts and H9c2 cells. Methods: Creatine Kinase - MB (CK-MB) and Lactate Dehydrogenase (LDH) levels were determined using commercial kits. Biochemical indices reflecting oxidative stress, such as catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also analyzed with commercial kits. Mitochondrial reactive oxygen species (ROS) 2’,7’-dichlorofluorescin diacetate (DCFH-DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes, and apoptosis was measured using a commercial kit. Western blots were used to detect the level of expression of cleaved caspase-3. Results: Doxorubicin treatment significantly increased oxidative stress levels, as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species. Doxorubicin also increased pathological damage in myocardial tissue, myocardial ROS levels, and malonyldialdehyde levels, and induced apoptosis in myocardial tissues and H9c2 cells. All of these doxorubicin-induced effects were attenuated by oxymatrine. Conclusion: These in vitro and in vivo findings indicate that oxymatrine may be a promising cardioprotective agent against doxorubicin-induced cardiotoxicity, at least in part mediated through oxymatrine’s inhibition of cardiac apoptosis and oxidative stress
研究领域:
药理学
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毒理学
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心脏病学
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肿瘤学
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DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2018
·Vol. 42
·期 11
·1584-1593
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IF 1.936
Bo Yu,Yanan Zhao,Hongli Zhang,Di Xie,Wei Nie,Kaiyao Shi
MicroRNA-143-3p (miR-143-3p) is involved in the initiation of inflammatory response and the progression of cardiovascular diseases. Myocardial hypertrophy is a common symptom in numerous cardiovascular diseases. In the current study, we attempted to demonstrate the role of miR-143-3p in the development of myocardial hypertrophy by focusing on its association with inflammation. Myocardial hypertrophy was induced by transverse aortic constriction (TAC) method in vivo and by H 2 O 2 administration in vitro. The expression status of miR-143-3p and downstream effectors were detected in animal heart tissues and H9c2 cells. Furthermore, the effect of miR-143-3p inhibition on H 2 O 2 -induced changes in ERK5/PPARδ/NF-κB axis was assessed. TAC induced oxidative stress and inflammation in rat heart tissues, which was associated with the increased expressions of miR-143-3p and p-ERK5. However, the up-regulated expression of miR-143-3p had no effect on the expression of ERK5, which was a direct target of miR-143-3p. The results of in vitro assays showed that H 2 O 2 administration increased the levels of miR-143-3p and p-EKR5 and induced the activation of NF-κB pathway. After the inhibition of miR-143-3p, the activation of EKR5 and NF-κB pathway was suppressed, whereas the expression of PPARδ was up-regulated. The current study demonstrated that miR-143-3p is crucial to the initiation of inflammatory response induced by myocardial hypertrophy. The activation of ERK5 following miR-143-3p up-regulation appears to be a complementary response to induce the subsequent anti-inflammatory signaling transduction, which needed further exploration.
研究领域:
心血管疾病
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分子生物学
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炎症
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Huihui Wang,Baoping Xie,Shuotao Shi,Rong Zhang,Qi Liang,Zhongqiu Liu,Yuanyuan Cheng
Myocardial infarction (MI) is a common disease with high morbidity and mortality. Curdione is a sesquiterpenoid from Radix Curcumae . The current study is aimed to investigate the protective effect and mechanism of curdione on ferroptosis in MI. Isoproterenol (ISO) was used to induce MI injury in mice and H9c2 cells. Curdione was orally given to mice once daily for 7 days. Echocardiography, biochemical kits, and western blotting were performed on the markers of cardiac ferroptosis. Curdione at 50 and 100 mg/kg significantly alleviated ISO-induced myocardial injury. Curdione and ferrostatin-1 significantly attenuated ISO-induced H9c2 cell injury. Curdione effectively suppressed cardiac ferroptosis, evidenced by decreasing malondialdehyde and iron contents, and increasing glutathione (GSH) level, GSH peroxidase 4 (GPX4), and ferritin heavy chain 1 expression. Importantly, drug affinity responsive target stability, molecular docking, and surface plasmon resonance technologies elucidated the direct target Keap1 of curdione. Curdione disrupted the interaction between Keap1 and thioredoxin1 (Trx1) but enhanced the Trx1/GPX4 complex. In addition, curdione-derived protection against ISO-induced myocardial ferroptosis was blocked after overexpression of Keap1, while enhanced after Keap1 silence in H9c2 cells. These findings demonstrate that curdione inhibited ferroptosis in ISO-induced MI via regulating Keap1/Trx1/GPX4 signaling pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF TOXICOLOGY
·
2024
·
IF 4.8
Wang Yanwei,Qiu Jingru,Yan Hua,Zhang Nan,Gao Shixuan,Xu Ning,Wang Cuiyan,Lou Haiyan
Doxorubicin (DOX) is one of the most frequently used chemotherapeutic drugs belonging to the class of anthracyclines. However, the cardiotoxic effects of anthracyclines limit their clinical use. Recent studies have suggested that ferroptosis is the main underlying pathogenetic mechanism of DOX-induced cardiomyopathy (DIC). BTB-and-CNC homology 1 (Bach1) acts as a key role in the regulation of ferroptosis. However, the mechanistic role of Bach1 in DIC remains unclear. Therefore, this study aimed to investigate the underlying mechanistic role of Bach1 in DOX-induced cardiotoxicity using the DIC mice in vivo (DOX at cumulative dose of 20 mg/kg) and the DOX-treated H9c2 cardiomyocytes in vitro (1 μM). Our results show a marked upregulation in the expression of Bach1 in the cardiac tissues of the DOX-treated mice and the DOX-treated cardiomyocytes. However, Bach1 −/− mice exhibited reduced lipid peroxidation and less severe cardiomyopathy after DOX treatment. Bach1 knockdown protected against DOX-induced ferroptosis in both in vivo and in vitro models. Ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, significantly alleviated DOX-induced cardiac damage. However, the cardioprotective effects of Bach1 knockdown were reversed by pre-treatment with Zinc Protoporphyrin (ZnPP), a selective inhibitor of heme oxygenase-1(HO-1). Taken together, these findings demonstrated that Bach1 promoted oxidative stress and ferroptosis through suppressing the expression of HO-1. Therefore, Bach1 may present as a promising new therapeutic target for the prevention and early intervention of DOX-induced cardiotoxicity.
研究领域:
药理学
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心脏病学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2022
·Vol. 101
·期 1
·24-39
·
IF 2.873
Donglin Zhang,Aiqin Pan,Jianke Gu,Renfeng Liao,Xueyu Chen,Zhaozhu Xu
MicroRNAs (miRs) are implicated in heart failure (HF). Thereby, we aim to uncover the role of miR-144-3p in HF. Doxorubicin (Dox)-induced HF model was constructed in rats and cardiomyocytes H9C2, and the cardiac function was determined using ultrasound cardiogram. Morphology of cardiac tissue was observed using hematoxylin–eosin (H&E) staining. The viability and apoptosis of Dox-treated and transfected cardiomyocytes were determined using Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Relative expressions of the HF-associated miRs (including miR-144-3p), suppressor of cytokine signaling 2 (SOCS2), apoptosis- and phosphoinositide 3-kinase (PI3K)/AKT pathway-related factors (B-cell lymphoma 2, Bcl-2; Bcl-2 associated X protein, Bax; cleaved [C] capsase-3; phosphoinositide 3-kinase, PI3K; phosphorylated-PI3K, p-PI3K; p-AKT; AKT) were measured with quantitative real-time polymerase chain reaction or Western blot. Target gene of miR-144-3p was predicted by Starbase and TargetScan and confirmed with dual-luciferase reporter assay. Dox caused rat cardiac dysfunction, aggravated cardiac injury, decreased cardiomyocytes viability, and the expression of miR-144-3p, Bcl-2, and phosphorylation of both PI3K and AKT yet the upregulated those of Bax and C caspase-3, which was reversed by upregulating miR-144-3p, whereas downregulating miR-144-3p did oppositely. SOCS2 was the target gene of miR-144-3p, Dox promoted SOCS2 expression, which was reversed by upregulating miR-144-3p, while downregulating miR-144-3p did conversely. In addition, silencing SOCS2 reversed the effects of miR-144-3p downregulation in Dox-treated cardiomyocytes. Upregulating miR-144-3p alleviated Dox-induced cardiac dysfunction and cell apoptosis via targeting SOCS2, providing a novel evidence of miR-144-3p in HF.
研究领域:
心脏病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2020
·Vol. 84
·期 4
·714-724
·
IF 1.516
Guo Xiao,Zhang Yongtao,Lu Changhong,Qu Fengxia,Jiang Xianyan
Heart failure (HF) is one of the most severe heart conditions, which lacks effective therapies. Therefore, it is necessary to develop more efficient drugs for HF. In this study, we investigated the cardioprotective effects of hyperoside against the pathological progression of HF. Thoracic aortic constriction (TAC) was performed to induce HF in rats. Hyperoside treatment improved cardiac function, decreased cardiomyocyte cross-sectional area and heart weight to body weight (HW/BW) ratio in HF rats. Moreover, hyperoside administration repressed apoptosis as evidenced by changing apoptosis-related protein levels, and promoted autophagy in TAC rats and angiotensin II (AngII)-induced H9C2 cells. Inhibition of autophagy by 3-methyladenine (3-MA) attenuated the beneficial effect of hyperoside against apoptosis in H9C2 cells. In summary, these data confirm that hyperoside effectively alleviates HF via suppressing apoptosis and inducing autophagy, which provides evidence that hyperoside may serve as a promising natural drug for treating HF.
研究领域:
心脏病学
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药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Yadong Zhang,Rui Wen,Jingyi Ren,Fan Zhang,Huanting Pei,Jinshi Zuo,Yuxia Ma
Introduction: Exposure to fine particulate matter (PM2.5) is known to be associated with cardiovascular diseases. Sesamin (Ses) is a natural phenolic compound found in sesame seeds and sesame oil. Ferroptosis is a novel mode of cell death characterised by iron-dependent lipid peroxidation. This study aims to explore whether PM2.5 can induce ferroptosis in H9C2 cells and to investigate the precise protective mechanism of Ses.Methods: Based on transcriptomic data, PM2.5 may induce ferroptosis in cardiomyocytes. The ferroptosis inducer erastin and ferroptosis inhibitor ferrostatin-1 (Fer-1) were used to illustrate the mechanisms involved in PM2.5-induced H9C2 cell injury. Using network pharmacology, the pharmacological mechanism and potential therapy targets of Ses were explored for the treatment of PM2.5-induced cardiomyocyte injury. H9C2 cells were cultured and pretreated with Fer-1 or different concentrations of Ses, and then cardiomyocyte injury model was established using erastin or PM2.5. Indicators of oxidative responses, including total superoxide dismutase, reduced glutathione, glutathione peroxidase and malondialdehyde, were measured. The expression levels of ferroptosis-related proteins were determined through Western blot analysis.Results: Results demonstrate that PM2.5 induces ferroptosis in H9C2 cells and Ses exerts a protective effect by suppressing ACSL4-mediated ferroptosis.Discussion: Overall, these findings elucidate a novel mechanism by which Ses ameliorates the detrimental effects of PM2.5 on cardiomyocytes.
研究领域:
心血管疾病
·
药理学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 23
·期 2
·1-10
·
IF 2.447
Xiaoqun Zhang,Xue Han,Yanan Zhang
Copine 3 (CPNE3) and receptor for activated C kinase 1 (RACK1) have been determined to be risk factors for patients with acute myocardial ischemia/reperfusion (I/R). The present study aimed to evaluate the role of CPNE3 and its interaction with RACK1 in myocardial (I/R) injury. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting were performed to detect CPNE3 and RACK1 expression levels in H9c2 cells before and after the transfection of CPNE3 overexpression plasmid or small interfering RNA‑RACK1. Cell viability was detected using a Cell Counting Kit‑8 assay, and immunoprecipitation assays were performed to determine the interaction between CPNE3 and RACK1. A commercial kit was used to examine lactate dehydrogenase (LDH) levels. The expression levels of inflammatory cytokines were detected via RT‑qPCR and western blotting. Cell apoptosis was assessed via TUNEL staining and western blotting. The results demonstrated that the expression levels of CPNE3 and RACK1 were decreased in hypoxia/reoxygenation (H/R)‑induced H9c2 cardiomyocytes, which was consistent with the expression levels observed in the myocardial I/R injury rat model. It was found that CPNE3 overexpression upregulated RACK1 expression, increased cell viability and suppressed the release of LDH in H/R‑induced H9c2 cells. Furthermore, CPNE3 overexpression inhibited the release of inflammatory cytokines and decreased cell apoptosis in H/R‑induced cardiomyocytes by activating RACK1 expression. The present study suggested that CPNE3 served an important role in preventing I/R injury by interacting with RACK1, providing novel insight into the prevention of myocardial I/R injury, as well as the treatment and care of patients with myocardial I/R.
研究领域:
心脏病学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Bo Yu,Dongna Liu,Hongli Zhang,Di Xie,Wei Nie,Kaiyao Shi,Ping Yang
Left ventricular hypertrophy (LVH) is a pathological characteristic shared by distinct heart disorders. Atorvastatin is employed as a lipid lowering agent and its heart protection effect has been recently reported as well. Thus, the current study attempted to validate the anti-hypertrophy effect of atorvastatin as well as the associated mechanism. Hypertrophic feature was induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using angiotensin II (Ang II). Then the animals and cells were treated with atorvastatin and the effect on cardiac weight and structure as well as cell viability, surface area, and apoptosis was assessed. The mechanism associated with the anti-hypertrophy effect of atorvastatin was further explored by focusing on the AMPK/Foxo1/miR-143-3p axis. The results showed that the administration of atorvastatin significantly suppressed TAC-induced heart weight increase and attenuated cardiac structure deteriorations in rats. In in vitro assays, atorvastatin increased cell viability, and reduced cell surface area and apoptosis in Ang II-treated H9c2 cells. At molecular level, atorvastatin activated AMPK, which further promoted Foxo1 activation and suppressed miR-143-3p level. The key role of AMPK during atorvastatin treatment was further validated by subjecting Ang II-treated H9c2 cells to co-incubation of atorvastatin and Compound C, which blocked the pro-survival and anti-hypertrophy effect of atorvastatin on H9c2 cells. The findings outlined in the current study confirmed the anti-hypertrophy effect of atorvastatin and provided a preliminary explanation on the mechanism associated with the treatment: the protective effect of atorvastatin on myocardium against hypertrophy depended on miR-143-3p inhibition via AMPK and Foxo1 activation.
研究领域:
心脏病学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
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