JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2026
·Vol. 40
·期 6
·e70946
·
IF 3.6
Lizhi Dai,Jingxuan Wang,Jia Liu,Zheyuan Cao,Yuhao Zhang,Youchong Li,Tong Yu,Jianhua Xiao
2-Ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant frequently detected in environmental matrices and poses potential health risks. However, its cardiotoxic effects on mammalian cardiomyocytes and the underlying molecular mechanisms remain largely unclear. Niacin (NIA), an essential water-soluble vitamin, exhibits potent antioxidant, anti-inflammatory, and mitochondrial-protective activities. In this study, we investigated EHDPHP-induced toxicity in H9C2 cardiomyocytes and the protective effects of NIA. Cells were exposed to 100 μM EHDPHP alone or in combination with 400, 600, and 800 μM NIA. EHDPHP exposure significantly reduced cell viability, disrupted the balance between pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) and the anti-inflammatory cytokine IL-10, and induced oxidative stress, as evidenced by elevated ROS, MitoSOX, and MDA levels alongside decreased activities of antioxidant enzymes (SOD, GSH, GSH-Px, and CAT). Additionally, EHDPHP disturbed mitochondrial dynamics by promoting fission and inhibiting fusion, impaired mitochondrial biogenesis via downregulation of AMPK and PGC-1α, triggered excessive mitophagy through PINK1, PRKN, and LC3 upregulation, and activated pyroptosis via GSDMD, NLRP3, and Caspase-1. Bioinformatics analyses confirmed the interconnected regulatory network among mitochondrial dynamics, mitophagy, pyroptosis, and inflammatory signaling in EHDPHP-induced cardiomyocyte injury. Notably, NIA intervention dose-dependently mitigated these detrimental effects, restoring cell viability, alleviating inflammation and oxidative stress, rebalancing mitochondrial fusion and fission, rescuing biogenesis, normalizing mitophagy, and inhibiting pyroptosis. These findings reveal a pathological cascade through which EHDPHP induces cardiomyocyte injury and demonstrate that NIA confers cardioprotection by targeting multiple pathological pathways. This study provides novel mechanistic insights into EHDPHP-induced cardiotoxicity and highlights NIA as a promising nutritional intervention for reducing cardiovascular risks associated with environmental pollutants.
✓ 已验证
DOI
PubMed
高影响因子
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
·
分子生物学
·
细胞生物学
✓ 已验证
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
·
心脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 12
·期 1
·88
·
IF 7.675
Shuo Han,Lifu Chen,Yi Zhang,Shihui Xie,Jiali Yang,Songkun Su,Hong Yao,Peiying Shi
Bee pollen possesses an anti-cardiomyocyte injury effect by reducing oxidative stress levels and inhibiting inflammatory response and apoptosis, but the possible effect mechanism has rarely been reported. This paper explores the effect of the extract of lotus bee pollen (LBPE) on cardiomyocyte hypertrophy (CH) and its mechanism. The main components of LBPE were identified via UPLC-QTOF MS. An isoproterenol-induced rat H9c2 CH model was subsequently used to evaluate the protection of LBPE on cells. LBPE (100, 250 and 500 μg∙mL−1) reduced the surface area, total protein content and MDA content, and increased SOD activity and GSH content in CH model in a dose-dependent manner. Meanwhile, quantitative real-time PCR trials confirmed that LBPE reduced the gene expression levels of CH markers, pro-inflammatory cytokines and pro-apoptosis factors, and increased the Bcl-2 mRNA expression and Bcl-2/Bax ratio in a dose-dependent manner. Furthermore, target fishing, bioinformatics analysis and molecular docking suggested JAK2 could be a pivotal target protein for the main active ingredients in the LBPE against CH. Ultimately, Western blot (WB) trials confirmed that LBPE can dose-dependently inhibit the phosphorylation of JAK2 and STAT3. The results show that LBPE can protect against ISO-induced CH, possibly via targeting the JAK2/STAT3 pathway, also suggesting that LBPE may be a promising candidate against CH.Keywords:lotus bee pollen extract;cardiomyocyte hypertrophy;JAK2/STAT3 signaling pathway;oxidative stress;inflammation
研究领域:
药理学
·
心脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
·
2021
·
IF 2.479
Fen Li,Jianguang Liu,Shifan Tang,Jie Yan,Haifeng Chen,Dongsheng Li,Xisheng Yan
Objective To investigate the effect and potential mechanism of quercetin on inflammation, oxidative stress, apoptosis, and mitochondrial structure and function in H9C2 cells. Materials and methods H9C2 cells were obtained from the Shanghai Institutes for Biological Sciences, Chinese Academy of Science, and randomly divided into six groups: control, model, PVT1 overexpression (OV), quercetin, OV + quercetin, and NAC groups. The CCK-8 assay was performed to examine cell proliferation. Flow cytometry was used to examine cell apoptosis, cell membrane potential, and ROS levels. The expression of endothelial nitric oxide synthase (eNOS), malondialdehyde (MDA), and superoxide dismutase (SOD) was measured by ELISA and a Biochemical kit. Western blotting was used to determine the levels of p-DRP1 (s637), MFN2, NF-kB, p-NF-kB, IkB, and p-IkB. IL-6, IL-10, TNF-α, and IL-1β mRNA expression was examined by RT-PCR. Electron microscopy was used to observe the structure of mitochondria in H9C2 cells. Results MDA, p-NF-κB, p-IKB, IL-6, IL-1β, and TNF-α expression levels, and the cell apoptosis rate were significantly higher in the model group than in the control group (P < 0.05). In contrast, the cell proliferation rate and IL-10, SOD, eNOS, and ATP levels were significantly lower in the model group (P < 0.05). Moreover, MDA expression was significantly lower in the OV, quercetin, quercetin + OV, and NAC groups than in the model group (P < 0.05), while SOD, eNOS, and ATP levels were higher. The electron microscopy results showed that PVT1 overexpression or quercetin treatment could inhibit inflammation-induced mitochondrial fission and promote mitochondrial fusion. Conclusion Quercetin promotes the proliferation of H9C2 cells, while inhibiting inflammation, oxidative stress, and cell apoptosis, and alleviating the structural and functional dysfunction of mitochondria. These effects are achieved by promoting PVT1 expression.
研究领域:
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Jing-yi Zhang,Ying Guo,Jin-ping Si,Xiao-bo Sun,Gui-bo Sun,Jing-jing Liu
Dendrobium officinale is one valuable traditional Chinese medicine, which has skyscraping medicinal value. Polysaccharide is the main active ingredient in D. officinale ; its antioxidant activity is a hot research topic nowadays. Oxidative stress plays an important role in the pathological progress of a variety of cardiovascular disease, as one of key factors of cardiomyocyte apoptosis. This research adopts a model of H 2 O 2 induction-H9c2 cardiomyocytes apoptosis, aiming to study the effect of Dendrobium officinale Polysaccharide (DOP-GY) for cardiomyocyte apoptosis caused by oxidative stress and its possible mechanism. Our results showed that pretreatment of DOP-GY (low dose: 6.25 μg/mL, medium dose: 12.5 μg/mL, high dose: 25 μg/mL) followed by a 2 h incubation with 200 μM H 2 O 2 elevated the survival rate, cutted the LDH leakage, reduced lipid peroxidation damage, improved the activity of the endogenous antioxidant enzymes. In addition, the pretreatment of DOP-GY significantly inhibited the production of ROS, declined of the mitochondrial membrane potential, down-regulated pro-apoptosis protein and up-regulated anti-apoptosis protein. The protective effect was correlated with the PI3K/Akt and MAPK signal pathway. Collectively, these observations suggest that DOY-GY has the potential to exert cardioprotective effects against H 2 O 2 -induced H9c2 cardiomyocyte apoptosis.
研究领域:
药理学
·
心脏病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 43
·期 2
·626-635
·
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
·
毒理学
·
心脏病学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF GENE MEDICINE
·
2020
·Vol. 22
·期 9
·e3201
·
IF 3.258
Liping Ma,Yanjing Cao,Lin Zhang,Ketao Li,Laixing Yan,Yizhan Pan,Jianhua Zhu
Background Celastrol (Cel) has been corroborated as an anti-inflammatory and anti-apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)-induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG-stimulated cardiomyocyte injury via regulating the miR-345-5p/growth arrest-specific 6 (Gas6) signaling pathway. Methods Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit-8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase-polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR-345-5p. Results The present study confirmed the inhibitory effects of Cel in HG-induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG-induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl-2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG-triggered repression of Gas6 protein expression, and Gas6 loss-of-function accelerated HG-induced cardiomyocyte apoptosis. HG-triggered up-regulation of miR-345-5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR-345-5p. Transfection with miR-345-5p inhibitors restrained HG-induced release of pro-inflammatory cytokines and cell apoptosis. Conclusions The findings of the present study demonstrate that Cel administration antagonized HG-induced cardiomyocyte apoptosis and inflammation through up-regulating Gas6 expression by restraining miR-345-5p.
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
International Heart Journal
·
2026
·Vol. 67
·期 1
·87-97
·
IF 1.3
Zhuyuan Liu,Yanru He,Chunshu Hao
Myocardial ischemia-reperfusion injury (MI/RI) refers to the deterioration of cardiac function after restoring ischemic myocardium perfusion. Stem cell exosomes have produced unique advantages in treating MI/RI. However, the roles of exosomal microRNA-223-3p (miR-223-3p) from adipose-derived stem cells (ADSCs) on MI/RI are still unclear. This study aimed to investigate the effects of exosomal miR-223-3p from ADSCs on hypoxia/reoxygenation (H/R)-induced H9c2 cell injuries. Our findings indicated that the separated ADSC-derived exosomes (ADSC-Exo) were spherical, with a complete cell membrane, an average diameter of 110 nm, and CD9 and CD63 expression. ADSC-Exo increased the cell viability, proliferation, glutathione (GSH) level, and glutathione peroxidase 4 (GPX4) and miR-223-3p expression and decreased the apoptosis, reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+ levels and acyl-CoA synthetase long chain family member 4 (ACSL4) and transferrin receptor (TFRC) expression of H9c2 cells. Overexpressing exosomal miR-223-3p from ADSCs further strengthened the effects of ADSC-Exo on H9c2 cells. Overexpressing TFRC in H9c2 cells effectively reversed the effects of miR-223-3p overexpressed ADSC-Exo on H9c2 cells. In addition, miR-223-3p targeted and negatively regulated TFRC. This study confirmed that exosomal miR-223-3p from ADSCs alleviated H/R-induced ferroptosis of H9c2 cells by inhibiting TFRC, providing a novel target and pathway for the clinical treatment of MI/RI.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2018
·Vol. 42
·期 11
·1584-1593
·
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
·
分子生物学
·
炎症
✓ 已验证
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
·
心脏病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 15
·2440
·
IF 4.7
Jingwen Yu,Xiangwei Xiao,Baiying Chen,Zeyuan Deng,Xuan Chen,Yawei Fan,Hongyan Li
The antioxidant activities of lycopene (LY), lutein (LU), chlorogenic acid (CA), and delphinidin (DP) were tested in vitro on H9c2 cell-based models. Some indicators, such as the generation of reactive oxygen (ROS), the quantification of cell antioxidant activity (CAA), and the expressions of SOD, GSH-Px, and CAT, were calculated to examine their antioxidant interactions. From our results, the phytochemical mixtures (M1: CA-LU: F3/10, M2: DP-CA: F7/10, M3: DP-LY: F5/10) displayed strong synergistic effects based on the generation of ROS and the quantification of CAA. However, great antagonistic bioactivities were seen in the combinations of LY-LU: F5/10 (M4), CA-LU: F9/10 (M5), and DP-LY: F7/10 (M6). Western blotting analysis indicated that the possible mechanism underlying the synergistic antioxidant interactions among phytochemical combinations was to enhance the accumulation of Nrf2 in the nucleus and the expression of its downstream antioxidant enzymes, HO-1 and GCLC. The combinations (M1–M3 groups) showed significant protection against the loss of mitochondrial membrane potential than individual groups to avoid excessive ROS production. The M4–M6 groups exerted antagonistic protective effects compared with the individual groups. In addition, lutein and lycopene absorption was improved more because of the presence of chlorogenic acid and delphinidin in the M1 and M3 groups, respectively. However, delphinidin significantly reduced the cellular uptake of lycopene in the M6 group. It appeared that antioxidant interactions of phytochemical combinations may contribute to the restoration of cellular redox homeostasis and lead to an improvement in diet quality and collocation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）