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Keywords = cardiomyoblasts

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25 pages, 3911 KiB  
Article
Genetic and Molecular Characterization of H9c2 Rat Myoblast Cell Line
by Thomas Liehr, Stefanie Kankel, Katharina S. Hardt, Eva M. Buhl, Heidi Noels, Diandra T. Keller, Sarah K. Schröder-Lange and Ralf Weiskirchen
Cells 2025, 14(7), 502; https://doi.org/10.3390/cells14070502 - 28 Mar 2025
Cited by 2 | Viewed by 1439
Abstract
This study presents a comprehensive genetic characterization of the H9c2 cell line, a widely used model for cardiac myoblast research. We established a short tandem repeat (STR) profile for H9c2 that is useful to confirm the identity and stability of the cell line. [...] Read more.
This study presents a comprehensive genetic characterization of the H9c2 cell line, a widely used model for cardiac myoblast research. We established a short tandem repeat (STR) profile for H9c2 that is useful to confirm the identity and stability of the cell line. Additionally, we prepared H9c2 metaphase chromosomes and performed karyotyping and molecular cytogenetics to further investigate chromosomal characteristics. The genetic analysis showed that H9c2 cells exhibit chromosomal instability, which may impact experimental reproducibility and data interpretation. Next-generation sequencing (NGS) was performed to analyze the transcriptome, revealing gene expression patterns relevant to cardiac biology. Western blot analysis further validated the expression levels of selected cardiac genes identified through NGS. Additionally, Phalloidin staining was used to visualize cytoskeletal organization, highlighting the morphological features of these cardiac myoblasts. Our findings collectively support that H9c2 cells are a reliable model for studying cardiac myoblast biology, despite some genetic alterations identified resembling sarcoma cells. The list of genes identified through NGS analysis, coupled with our comprehensive genetic analysis, will serve as a valuable resource for future studies utilizing this cell line in cardiovascular medicine. Full article
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16 pages, 3927 KiB  
Article
Sinapic Acid Ameliorates Doxorubicin-Induced Cardiotoxicity in H9c2 Cardiomyoblasts by Inhibiting Oxidative Stress Through Activation of the Nrf2 Signaling Pathway
by Tsendsuren Tungalag, Hyung-Sub Kang and Dong Kwon Yang
Antioxidants 2025, 14(3), 337; https://doi.org/10.3390/antiox14030337 - 13 Mar 2025
Cited by 1 | Viewed by 939
Abstract
The use of doxorubicin (Dox) is restricted because of its cardiotoxicity, which poses a significant mortality risk for cancer patients, despite being a highly effective antibiotic for treating various types of cancer. Therefore, identifying substances or developing preventive strategies against Dox-induced cardiotoxicity is [...] Read more.
The use of doxorubicin (Dox) is restricted because of its cardiotoxicity, which poses a significant mortality risk for cancer patients, despite being a highly effective antibiotic for treating various types of cancer. Therefore, identifying substances or developing preventive strategies against Dox-induced cardiotoxicity is crucial. This study was conducted to determine whether sinapic acid (SA), a phenolic compound with a range of pharmacological effects, could protect against Dox-induced cardiotoxicity in H9c2 cardiomyoblasts. To investigate the preventive effect of SA, H9c2 cardiomyoblasts treated with Dox were pretreated with SA at various concentrations. SA effectively rescued the cells from Dox-induced cardiotoxicity. Additionally, SA significantly reduced oxidative stress by inhibiting mitochondrial dysfunction and endoplasmic reticulum stress. SA also suppressed the expression of MAPK proteins. As for the underlying mechanism of SA’s protective effect against Dox-induced cardiotoxicity, SA activated nuclear factor erythroid-2-related factor (Nrf2) by facilitating its movement from the cytosol to the nucleus and increasing the expression of its target antioxidative genes. In summary, this study demonstrated that SA protects H9c2 cardiomyoblasts from Dox-induced cardiotoxicity by inhibiting oxidative stress by the activation of Nrf2-related signaling pathway. Our findings enhance the development of therapeutic strategies to mitigate cardiac toxicity caused by Dox, highlighting the potential antioxidant effect of SA in Dox-treated H9c2 cardiomyoblasts. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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16 pages, 3048 KiB  
Article
Lipid Emulsion Mitigates the Cardiotoxic Effects of Labetalol in Rat Cardiomyoblasts
by Gyujin Sim, Seong-Ho Ok, Soo Hee Lee, Kyeong-Eon Park, Seunghyeon Park and Ju-Tae Sohn
Cells 2025, 14(3), 187; https://doi.org/10.3390/cells14030187 - 26 Jan 2025
Viewed by 822
Abstract
Lipid emulsion has recently emerged as an effective agent for improving the cardiotoxicity of highly lipophilic drugs. However, its effect on cardiotoxicity induced by labetalol, a nonselective beta-blocker, remains unknown. In this study, we investigated the effects of lipid emulsion on the cardiotoxicity [...] Read more.
Lipid emulsion has recently emerged as an effective agent for improving the cardiotoxicity of highly lipophilic drugs. However, its effect on cardiotoxicity induced by labetalol, a nonselective beta-blocker, remains unknown. In this study, we investigated the effects of lipid emulsion on the cardiotoxicity of labetalol in rat cardiomyoblasts and tried to decipher the underlying mechanisms. The effects of lipid emulsion on labetalol-induced changes in cell viability, expression of Bax/Bcl-2, cleaved caspase-3, and cleaved caspase-9, and phosphorylation of GSK-3β, Akt, and PI3K were examined. Lipid emulsion inhibited labetalol-induced decrease in cell viability, whereas LY294002, MK2206, and SB216763, the inhibitors of phosphoinositide 3-kinase (PI3K), Akt, glycogen synthase kinase-3β (GSK-3β), respectively, partially attenuated this restoration of cell viability. Lipid emulsion reversed the increase in expression of cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 and decrease in the phosphorylation of GSK-3β, Akt, and PI3K by labetalol. Lipid emulsion and cyclosporin, a mitochondrial permeability transition pore (MPTP) inhibitor, reduced the labetalol-induced increase in the number of TUNEL-positive cells and promoted late-stage apoptosis. Overall, lipid emulsion inhibited apoptotic cell death caused by labetalol toxicity via the inhibition of intrinsic apoptotic pathway and MPTP in rat cardiomyoblasts, which appears to involve PI3K, Akt, and GSK-3β signaling pathways. Full article
(This article belongs to the Section Cells of the Cardiovascular System)
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14 pages, 2345 KiB  
Article
The Protective Role of miR-130b-3p Against Palmitate-Induced Lipotoxicity in Cardiomyocytes Through PPARγ Pathway
by Elena Alonso-Villa, Alipio Mangas, Fernando Bonet, Óscar Campuzano, Maribel Quezada-Feijoo, Mónica Ramos, Carlos García-Padilla, Diego Franco and Rocio Toro
Int. J. Mol. Sci. 2024, 25(22), 12161; https://doi.org/10.3390/ijms252212161 - 13 Nov 2024
Cited by 3 | Viewed by 1545
Abstract
Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPARγ) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPARγ causes dilated cardiomyopathy [...] Read more.
Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPARγ) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPARγ causes dilated cardiomyopathy associated with lipotoxicity in mice. miR-130b-3p has been shown to be downregulated in the plasma of idiopathic dilated cardiomyopathy patients, but its role in modulating cardiomyocyte lipotoxicity via PPARγ remains unclear. Our objective was to investigate the protective role of miR-130b-3p against palmitate-induced lipotoxicity in cardiomyocytes through the modulation of the PPARγ signaling pathway. Human cardiomyoblasts were treated with palmitate. Intracellular lipid accumulation and expression of PPARγ and its downstream targets (CD36, FABP3, CAV1, VLDLR) were analyzed. Mitochondrial oxidative stress was assessed via MitoTracker Green and Redox Sensor Red staining and expression of CPT1B and SOD2. Endoplasmic reticulum stress and apoptosis were determined by examining GRP78, ATF6, XBP1s, CHOP, and caspase-3 expression. miR-130b-3p overexpression was achieved using transfection methods, and its effect on these parameters was evaluated. Luciferase assays were used to confirm PPARγ as a direct target of miR-130b-3p. Palmitate treatment led to increased lipid accumulation and upregulation of PPARγ and its downstream targets in human cardiomyoblasts. Palmitate also increased mitochondrial oxidative stress, endoplasmic reticulum stress and apoptosis. miR-130b-3p overexpression reduced PPARγ expression and its downstream signaling, alleviated mitochondrial oxidative stress and decreased endoplasmic reticulum stress and apoptosis in palmitate-stimulated cardiomyoblasts. Luciferase assays confirmed PPARγ as a direct target of miR-130b-3p. Our findings suggest that miR-130b-3p plays a protective role against palmitate-induced lipotoxicity in cardiomyocytes by modulating the PPARγ signaling pathway. Full article
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18 pages, 3034 KiB  
Article
Influence of Anesthetic Regimes on Extracellular Vesicles following Remote Ischemic Preconditioning in Coronary Artery Disease
by Phuong N. V. Pham, Loubna Yahsaly, Crista Ochsenfarth, Bernd Giebel, Romina Schnitzler, Peter Zahn and Ulrich H. Frey
Int. J. Mol. Sci. 2024, 25(17), 9304; https://doi.org/10.3390/ijms25179304 - 28 Aug 2024
Cited by 1 | Viewed by 1770
Abstract
Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on [...] Read more.
Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 ± 435.6 pg/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 ± 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism. Full article
(This article belongs to the Collection Feature Papers in “Molecular Biology”)
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14 pages, 1135 KiB  
Article
Synthesis and Biological Activity of Homohypotaurine Obtained by the Enzyme-Based Conversion of Homocysteine Sulfinic Acid Using Recombinant Escherichia Coli Glutamate Decarboxylase
by Mario Fontana, Aysenur Gunaydin Akyildiz, Chiara D’Alonzo, Fabio Giovannercole, Arianna Zicchi, Antonio Francioso, Elisabetta Capuozzo and Daniela De Biase
Molecules 2024, 29(17), 3985; https://doi.org/10.3390/molecules29173985 - 23 Aug 2024
Cited by 1 | Viewed by 1688
Abstract
l-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the l-homocysteine thiol [...] Read more.
l-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the l-homocysteine thiol group and its decarboxylation on C-alpha lead to the formation of l-homocysteinesulfinic acid (l-HCSA) and homohypotaurine (HHT), respectively. Both compounds are not readily available from commercial suppliers, which hinders the investigation of their biological activities. Herein, the chemical synthesis of l-HCSA, from l-homocystine, was the starting point for establishing the bio-based synthesis of HHT using recombinant Escherichia coli glutamate decarboxylase (EcGadB), an enzyme already successfully employed for the bio-based synthesis of GABA and its phosphinic analog. Prior to HHT synthesis, kcat (33.92 ± 1.07) and KM (38.24 ± 3.45 mM) kinetic constants were determined for l-HCSA on EcGadB. The results of our study show that the EcGadB-mediated synthesis of HHT can be achieved with good yields (i.e., 40% following enzymatic synthesis and column chromatography). Purified HHT was tested in vitro on primary human umbilical vein endothelial cells and rat cardiomyoblasts and compared to the fully oxidized analog, homotaurine (OT, also known as tramiprosate), in widespread pharmaceutical use. The results show that both cell lines display statistically significant recovery from the cytotoxic effects induced by H2O2 in the presence of HHT. Full article
(This article belongs to the Special Issue Enzymes in Biosynthesis and Biocatalysis)
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20 pages, 13527 KiB  
Article
Caprylic Acid Inhibits High Mobility Group Box-1-Induced Mitochondrial Damage in Myocardial Tubes
by Shota Nukaga, Rina Fujiwara-Tani, Ryoichi Nishida, Yoshihiro Miyagawa, Kei Goto, Isao Kawahara, Chie Nakashima, Kiyomu Fujii, Ruiko Ogata, Hitoshi Ohmori and Hiroki Kuniyasu
Int. J. Mol. Sci. 2024, 25(15), 8081; https://doi.org/10.3390/ijms25158081 - 24 Jul 2024
Cited by 2 | Viewed by 1510
Abstract
Myocardial damage significantly impacts the prognosis of patients with cancer; however, the mechanisms of myocardial damage induced by cancer and its treatment remain unknown. We previously reported that medium-chain fatty acids (MCFAs) improve cancer-induced myocardial damage but did not evaluate the differences in [...] Read more.
Myocardial damage significantly impacts the prognosis of patients with cancer; however, the mechanisms of myocardial damage induced by cancer and its treatment remain unknown. We previously reported that medium-chain fatty acids (MCFAs) improve cancer-induced myocardial damage but did not evaluate the differences in effect according to MCFA type. Therefore, this study investigated the role of inflammatory cytokines in cancer-induced myocardial damage and the effects of three types of MCFAs (caprylic acid [C8], capric acid [C10], and lauric acid [C12]). In a mouse model, the C8 diet showed a greater effect on improving myocardial damage compared with C10 and C12 diets. Myocardial tubes differentiated from H9C2 cardiomyoblasts demonstrated increased mitochondrial oxidative stress, decreased membrane potential and mitochondrial volume, and inhibited myocardial tube differentiation following treatment with high-mobility group box-1 (HMGB1) but not interleukin-6 and tumor necrosis factor-α cytokines. However, HMGB1 treatment combined with C8 improved HMGB1-induced mitochondrial damage, enhanced autophagy, and increased mitochondrial biogenesis and maturation. However, these effects were only partial when combined with beta-hydroxybutyrate, a C8 metabolite. Thus, HMGB1 may play an important role in cancer-related myocardial damage. C8 counteracts HMGB1’s effects and improves cancer-related myocardial damage. Further clinical studies are required to investigate the effects of C8. Full article
(This article belongs to the Special Issue Role of Natural Products in Health and Diseases)
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13 pages, 4705 KiB  
Article
PM2.5 Induces Cardiomyoblast Senescence via AhR-Mediated Oxidative Stress
by Tiantian Liu, Bin Jiang, Baoqiang Fu, Changyi Shang, Haobin Feng, Tao Chen and Yan Jiang
Antioxidants 2024, 13(7), 786; https://doi.org/10.3390/antiox13070786 - 28 Jun 2024
Cited by 11 | Viewed by 2068
Abstract
Previous research has established a correlation between PM2.5 exposure and aging-related cardiovascular diseases, primarily in blood vessels. However, the impact of PM2.5 on cardiomyocyte aging remains unclear. In this study, we observed that extractable organic matter (EOM) from PM2.5 exposure led to cellular [...] Read more.
Previous research has established a correlation between PM2.5 exposure and aging-related cardiovascular diseases, primarily in blood vessels. However, the impact of PM2.5 on cardiomyocyte aging remains unclear. In this study, we observed that extractable organic matter (EOM) from PM2.5 exposure led to cellular senescence in H9c2 cardiomyoblast cells, as characterized by an increase in the percentage of β-galactosidase-positive cells, elevated expression levels of p16 and p21, and enhanced H3K9me3 foci. EOM also induced cell cycle arrest at the G1/S stage, accompanied by downregulation of CDK4 and Cyclin D1. Furthermore, EOM exposure led to a significant elevation in intracellular reactive oxygen species (ROS), mitochondrial ROS, and DNA damage. Supplementation with the antioxidant NAC effectively attenuated EOM-induced cardiac senescence. Our findings also revealed that exposure to EOM activated the aryl hydrocarbon receptor (AhR) signaling pathway, as evidenced by AhR translocation to the nucleus and upregulation of Cyp1a1 and Cyp1b1. Importantly, the AhR antagonist CH223191 effectively mitigated EOM-induced oxidative stress and cellular senescence. In conclusion, our results indicate that PM2.5-induced AhR activation leads to oxidative stress, DNA damage, and cell cycle arrest, leading to cardiac senescence. Targeting the AhR/ROS axis might be a promising therapeutic strategy for combating PM2.5-induced cardiac aging. Full article
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14 pages, 2955 KiB  
Article
The Proteoglycans Biglycan and Decorin Protect Cardiac Cells against Irradiation-Induced Cell Death by Inhibiting Apoptosis
by Renáta Gáspár, Petra Diószegi, Dóra Nógrádi-Halmi, Barbara Erdélyi-Furka, Zoltán Varga, Zsuzsanna Kahán and Tamás Csont
Cells 2024, 13(10), 883; https://doi.org/10.3390/cells13100883 - 20 May 2024
Cited by 1 | Viewed by 2123
Abstract
Radiation-induced heart disease (RIHD), a common side effect of chest irradiation, is a primary cause of mortality among patients surviving thoracic cancer. Thus, the development of novel, clinically applicable cardioprotective agents which can alleviate the harmful effects of irradiation on the heart is [...] Read more.
Radiation-induced heart disease (RIHD), a common side effect of chest irradiation, is a primary cause of mortality among patients surviving thoracic cancer. Thus, the development of novel, clinically applicable cardioprotective agents which can alleviate the harmful effects of irradiation on the heart is of great importance in the field of experimental oncocardiology. Biglycan and decorin are structurally related small leucine-rich proteoglycans which have been reported to exert cardioprotective properties in certain cardiovascular pathologies. Therefore, in the present study we aimed to examine if biglycan or decorin can reduce radiation-induced damage of cardiomyocytes. A single dose of 10 Gray irradiation was applied to induce radiation-induced cell damage in H9c2 cardiomyoblasts, followed by treatment with either biglycan or decorin at various concentrations. Measurement of cell viability revealed that both proteoglycans improved the survival of cardiac cells post-irradiation. The cardiocytoprotective effect of both biglycan and decorin involved the alleviation of radiation-induced proapoptotic mechanisms by retaining the progression of apoptotic membrane blebbing and lowering the number of apoptotic cell nuclei and DNA double-strand breaks. Our findings provide evidence that these natural proteoglycans may exert protection against radiation-induced damage of cardiac cells. Full article
(This article belongs to the Special Issue Focus on Machinery of Cell Death)
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15 pages, 3236 KiB  
Article
Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1
by Kei Goto, Rina Fujiwara-Tani, Shota Nukaga, Yoshihiro Miyagawa, Isao Kawahara, Ryoichi Nishida, Ayaka Ikemoto, Rika Sasaki, Ruiko Ogata, Shingo Kishi, Yi Luo, Kiyomu Fujii, Hitoshi Ohmori and Hiroki Kuniyasu
Int. J. Mol. Sci. 2024, 25(9), 4735; https://doi.org/10.3390/ijms25094735 - 26 Apr 2024
Cited by 1 | Viewed by 1833
Abstract
Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat [...] Read more.
Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system. Full article
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17 pages, 3674 KiB  
Article
Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene
by Kiyomu Fujii, Rina Fujiwara-Tani, Shota Nukaga, Hitoshi Ohmori, Yi Luo, Ryoichi Nishida, Takamitsu Sasaki, Yoshihiro Miyagawa, Chie Nakashima, Isao Kawahara, Ruiko Ogata, Ayaka Ikemoto, Rika Sasaki and Hiroki Kuniyasu
Int. J. Mol. Sci. 2024, 25(5), 3015; https://doi.org/10.3390/ijms25053015 - 5 Mar 2024
Cited by 3 | Viewed by 2311
Abstract
Patients with cancer die from cardiac dysfunction second only to the disease itself. Cardiotoxicity caused by anticancer drugs has been emphasized as a possible cause; however, the details remain unclear. To investigate this mechanism, we treated rat cardiomyoblast H9c2 cells with sunitinib, lapatinib, [...] Read more.
Patients with cancer die from cardiac dysfunction second only to the disease itself. Cardiotoxicity caused by anticancer drugs has been emphasized as a possible cause; however, the details remain unclear. To investigate this mechanism, we treated rat cardiomyoblast H9c2 cells with sunitinib, lapatinib, 5-fluorouracil, and cisplatin to examine their effects. All anticancer drugs increased ROS, lipid peroxide, and iron (II) levels in the mitochondria and decreased glutathione peroxidase-4 levels and the GSH/GSSG ratio. Against this background, mitochondrial iron (II) accumulates through the unregulated expression of haem oxygenase-1 and ferrochelatase. Anticancer-drug-induced cell death was suppressed by N-acetylcysteine, deferoxamine, and ferrostatin, indicating ferroptosis. Anticancer drug treatment impairs mitochondrial DNA and inhibits oxidative phosphorylation in H9c2 cells. Similar results were observed in the hearts of cancer-free rats treated with anticancer drugs in vitro. In contrast, treatment with pterostilbene inhibited the induction of ferroptosis and rescued the energy restriction induced by anticancer drugs both in vitro and in vivo. These findings suggest that induction of ferroptosis and inhibition of oxidative phosphorylation are mechanisms by which anticancer drugs cause myocardial damage. As pterostilbene ameliorates these mechanisms, it is expected to have significant clinical applications. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress 2.0)
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17 pages, 4584 KiB  
Article
Downregulation of Mitochondrial Fusion Protein Expression Affords Protection from Canonical Necroptosis in H9c2 Cardiomyoblasts
by Yuki Toda, Sang-Bing Ong, Toshiyuki Yano, Atsushi Kuno, Hidemichi Kouzu, Tatsuya Sato, Wataru Ohwada, Yuki Tatekoshi, Toshifumi Ogawa, Masaki Shimizu, Masaya Tanno and Masato Furuhashi
Int. J. Mol. Sci. 2024, 25(5), 2905; https://doi.org/10.3390/ijms25052905 - 2 Mar 2024
Cited by 6 | Viewed by 2230
Abstract
Necroptosis, a form of necrosis, and alterations in mitochondrial dynamics, a coordinated process of mitochondrial fission and fusion, have been implicated in the pathogenesis of cardiovascular diseases. This study aimed to determine the role of mitochondrial morphology in canonical necroptosis induced by a [...] Read more.
Necroptosis, a form of necrosis, and alterations in mitochondrial dynamics, a coordinated process of mitochondrial fission and fusion, have been implicated in the pathogenesis of cardiovascular diseases. This study aimed to determine the role of mitochondrial morphology in canonical necroptosis induced by a combination of TNFα and zVAD (TNF/zVAD) in H9c2 cells, rat cardiomyoblasts. Time-course analyses of mitochondrial morphology showed that mitochondria were initially shortened after the addition of TNF/zVAD and then their length was restored, and the proportion of cells with elongated mitochondria at 12 h was larger in TNF/zVAD-treated cells than in non-treated cells (16.3 ± 0.9% vs. 8.0 ± 1.2%). The knockdown of dynamin-related protein 1 (Drp1) and fission 1, fission promoters, and treatment with Mdivi-1, a Drp-1 inhibitor, had no effect on TNF/zVAD-induced necroptosis. In contrast, TNF/zVAD-induced necroptosis was attenuated by the knockdown of mitofusin 1/2 (Mfn1/2) and optic atrophy-1 (Opa1), proteins that are indispensable for mitochondrial fusion, and the attenuation of necroptosis was not canceled by treatment with Mdivi-1. The expression of TGFβ-activated kinase (TAK1), a negative regulator of RIP1 activity, was upregulated and the TNF/zVAD-induced RIP1-Ser166 phosphorylation, an index of RIP1 activity, was mitigated by the knockdown of Mfn1/2 or Opa1. Pharmacological TAK1 inhibition attenuated the protection afforded by Mfn1/2 and Opa1 knockdown. In conclusion, the inhibition of mitochondrial fusion increases TAK1 expression, leading to the attenuation of canonical necroptosis through the suppression of RIP1 activity. Full article
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12 pages, 1957 KiB  
Article
Comparison of the Protective Effects of Nebivolol and Metoprolol against LPS-Induced Injury in H9c2 Cardiomyoblasts
by Rukhsana Gul, Meshail Okla, Amer Mahmood, Shahid Nawaz, Amina Fallata, Arwa Bazighifan, Musaad Alfayez and Assim A. Alfadda
Curr. Issues Mol. Biol. 2023, 45(11), 9316-9327; https://doi.org/10.3390/cimb45110583 - 20 Nov 2023
Cited by 2 | Viewed by 1940
Abstract
Here, we, for the first time, compared the cardioprotective effects of third-generation vasodilating beta-blocker nebivolol (Neb) and conventional beta-blocker metoprolol (Met) on LPS-induced injury in H9c2 cardiomyoblasts. Our findings denoted that Neb and Met pretreatment diminish LPS-mediated cytotoxicity and oxidative stress. Concomitantly, LPS-triggered [...] Read more.
Here, we, for the first time, compared the cardioprotective effects of third-generation vasodilating beta-blocker nebivolol (Neb) and conventional beta-blocker metoprolol (Met) on LPS-induced injury in H9c2 cardiomyoblasts. Our findings denoted that Neb and Met pretreatment diminish LPS-mediated cytotoxicity and oxidative stress. Concomitantly, LPS-triggered inflammatory cytokines activation was significantly suppressed by Neb but not by Met. Pretreatment with either Neb or Met alleviated LPS-mediated mitochondrial impairment by enhancing the expression of genes related to its biogenesis such as PGC-1α, NRF1, and TFAM. On the contrary, Neb but not Met-upregulated mitochondrial fusion-related genes such as OPA, and MFN2. In summary, our findings suggest that Neb and Met treatment significantly ameliorated the LPS-induced cytotoxicity and oxidative stress. Additionally, these findings suggest that Neb but not Met significantly down-regulates LPS-induced proinflammatory factors, probably by enhancing mitochondrial biogenesis and fusion. Full article
(This article belongs to the Special Issue Mitochondrial Function and Dysfunction)
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14 pages, 1618 KiB  
Article
Insights on Juniperus phoenicea Essential Oil as Potential Anti-Proliferative, Anti-Tyrosinase, and Antioxidant Candidate
by Rim Ben Mansour, Hanen Wasli, Soumaya Bourgou, Saber Khamessi, Riadh Ksouri, Wided Megdiche-Ksouri and Susana M. Cardoso
Molecules 2023, 28(22), 7547; https://doi.org/10.3390/molecules28227547 - 11 Nov 2023
Cited by 10 | Viewed by 3068
Abstract
In this study, the anti-cancer, anti-tyrosinase, and antioxidant activities of essential oils (EOs) of berries and leaves of Juniperus phoenicea grown wild in North of Tunisia were investigated. The EO yields from leaves and berries were 1.69% and 0.45%, respectively. GC-MS analysis revealed [...] Read more.
In this study, the anti-cancer, anti-tyrosinase, and antioxidant activities of essential oils (EOs) of berries and leaves of Juniperus phoenicea grown wild in North of Tunisia were investigated. The EO yields from leaves and berries were 1.69% and 0.45%, respectively. GC-MS analysis revealed that α-pinene is the predominant component in both EOs (44.17 and 83.56%, respectively). Leaves essential oil presented high levels of β-phellandrene (18%) and camphene (15%). The EOs displayed cytotoxic effects against MCF-7 breast cancer cell, HT-29 colon cancer, and the normal cells H9C2 cardiomyoblasts. Leaves oil strongly inhibited colon cell line proliferation (IC50 of 38 µg/mL), while berries essential oil was more potent against breast cancerous cells MCF-7 (IC50 of 60 µg/mL). Interestingly, berries essential oil exhibited high ability to inhibit melanin synthesis by inhibiting enzyme mono and diphenolase activities. Overall, the results suggested that the two oils are significant sources of healthy natural chemicals. Full article
(This article belongs to the Special Issue Essential Oils in Human Health)
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19 pages, 4611 KiB  
Article
Doxorubicin-Induced Cardiomyopathy: A Preliminary Study on the Cardioprotective Benefits of 7-Hydroxyflavanone
by Nonhlakanipho F. Sangweni, Kwazi Gabuza, Ruzayda van Aarde, Lawrence Mabasa, Derick van Vuuren, Barbara Huisamen, Reenen Barry and Rabia Johnson
Int. J. Mol. Sci. 2023, 24(20), 15395; https://doi.org/10.3390/ijms242015395 - 20 Oct 2023
Cited by 3 | Viewed by 1861
Abstract
The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC [...] Read more.
The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC was established by exposing H9c2 cardiomyoblasts to Dox for 6 days. Similarly, cells were also co-treated with 7H to assess its ability to mitigate DIC. The data obtained indicate that 7H, as a co-treatment, alleviates Dox-induced oxidative stress by enhancing total glutathione content (p ≤ 0.001) and superoxide dismutase activity (p ≤ 0.001) whilst decreasing ROS (p ≤ 0.001), malondialdehyde production (p ≤ 0.001) and the secretion of interleukin-6 (p ≤ 0.001). The data also showed an improvement in mitochondrial function as shown via enhanced bioenergetics, mitochondrial membrane potential, and PGC1-alpha (p ≤ 0.05) and pAMPK (p ≤ 0.001) expression. The cardioprotective potential of 7H was further highlighted by its ability attenuate Dox-induced caspase 3/7 activity (p ≤ 0.001), apoptosis (p ≤ 0.001) and necrosis (p ≤ 0.05). In conclusion, our findings demonstrated the cardioprotective benefits of 7H and thus suggests that it could be a suitable candidate cardioprotective agent against DIC. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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