Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells

Guo, Runmin; Xu, Wei; Lin, Jianwen; Mo, Liqiu; Hua, Xin; Chen, Pei-Xi; Wu, Keng; Zheng, Duo; Feng, Jianqiang

doi:10.3892/mmr.2013.1554

Cited by 113 publications

(89 citation statements)

References 37 publications

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“…The ability of naringin to arrest the DOX-induced attrition in GSH, GST, catalase and SOD may have subsequently reduced the lipid peroxidation by reducing the oxidation of cellular lipids. At molecular level, the DOX has been reported to increase the activation of NF-κB and COX-II in cardiomyocytes [12,62,63] and inhibition of NF-κB and COX-II by naringin may have suppressed the inflammation and reduced the DOX-induced hepatotoxicity in the present study. Naringin has been reported to suppress the transcription of NF-κB and COX-II in vitro [64].…”

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 53%

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

Ch¹,

Jagetia²,

Lalnuntluangi³

2016

Biochem Mol Biol J

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Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 53%

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

Ch¹,

Jagetia²,

Lalnuntluangi³

2016

Biochem Mol Biol J

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“…For example, Liu et al (2008) reported observing increased p-ERK1/2 but unchanged p-JNK and p-P38 in DOX-treated H9c2 cells. In another report, P38 MAPK was demonstrated to contribute to DOX-induced inflammation and cytotoxicity in H9c2 cardiac cells (Guo et al, 2013). These findings might be attributed to the regulation of MAPK being dependent on the time of DOX treatment and the different experimental conditions used.…”

Section: Discussionmentioning

confidence: 89%

Ophiopogonin D Attenuates Doxorubicin-Induced Autophagic Cell Death by Relieving Mitochondrial Damage In Vitro and In Vivo

Zhang

Meng

Zhang

et al. 2014

J Pharmacol Exp Ther

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It has been reported that ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from Ophiopogon japonicas, promotes antioxidative protection of the cardiovascular system. However, it is unknown whether OP-D exerts protective effects against doxorubicin (DOX)-induced autophagic cardiomyocyte injury. Here, we demonstrate that DOX induced excessive autophagy through the generation of reactive oxygen species (ROS) in H9c2 cells and in mouse hearts, which was indicated by a significant increase in the number of autophagic vacuoles, LC3-II/LC3-I ratio, and upregulation of the expression of GFP-LC3. Pretreatment with OP-D partially attenuated the above phenomena, similar to the effects of treatment with 3-methyladenine. In addition, OP-D treatment significantly relieved the disruption of the mitochondrial membrane potential by antioxidative effects through downregulating the expression of both phosphorylated c-Jun N-terminal kinase and extracellular signal-regulated kinase. The ability of OP-D to reduce the generation of ROS due to mitochondrial damage and, consequently, to inhibit autophagic activity partially accounts for its protective effects in the hearts against DOX-induced toxicity.

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“…Among these, the nuclear translocation of the p65 subunit is a key step in the activation of NF-κB (13). NF-κB is known to be activated by p38 MAPK (a member of the MAPK family) in cardiomyocytes (14)(15)(16). Accumulating evidence indicates that NF-κB plays a significant role in cardiac damage induced by various stimuli (14)(15)(16).…”

Section: Exogenous H 2 S Protects H9c2 Cardiac Cells Against High Glumentioning

confidence: 99%

“…NF-κB is known to be activated by p38 MAPK (a member of the MAPK family) in cardiomyocytes (14)(15)(16). Accumulating evidence indicates that NF-κB plays a significant role in cardiac damage induced by various stimuli (14)(15)(16). Guo et al demonstrated the involvement of the NF-κB pathway in doxorubicin-induced cardiac cytotoxicity, resulting in a decrease in cell viability (14,15).…”

Section: Exogenous H 2 S Protects H9c2 Cardiac Cells Against High Glumentioning

confidence: 99%

“…Accumulating evidence indicates that NF-κB plays a significant role in cardiac damage induced by various stimuli (14)(15)(16). Guo et al demonstrated the involvement of the NF-κB pathway in doxorubicin-induced cardiac cytotoxicity, resulting in a decrease in cell viability (14,15). The NF-κB pathway has also been implicated in G-protein-coupled receptor angonist-elicited cardiomyocyte hypertrophy (16).…”

Section: Exogenous H 2 S Protects H9c2 Cardiac Cells Against High Glumentioning

confidence: 99%

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Exogenous H2S protects H9c2 cardiac cells against high glucose-induced injury and inflammation by inhibiting the activation of the NF-κB and IL-1β pathways

Chen

Lin

et al. 2014

International Journal of Molecular Medicine

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Abstract. Hyperglycemia has been reported to activate the nuclear factor-κB (NF-κB) pathway. We have previously demonstrated that exogenous hydrogen sulfide (H 2 S) protects cardiomyocytes against high glucose (HG)-induced injury by inhibiting the activity of p38 mitogen-activated protein kinase (MAPK), which can activate the NF-κB pathway and induce interleukin (IL)-1β production. In the present study, we aimed to investigate the hypothesis that exogenous H 2 S protects cardiomyocytes against HG-induced injury and inflammation through the inhibition of the NF-κB/IL-1β pathway. H9c2 cardiac cells were treated with 35 mM glucose (HG) for 24 h to establish a model of HG-induced damage. Our results demonstrated that treatment of the cells with 400 µM sodium hydrogen sulfide (NaHS, a donor of H 2 S) or 100 µM pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) for 30 min prior to exposure to HG markedly attenuated the HG-induced increase in the expression levels of the phosphorylated (p)-NF-κB p65 subunit. Notably, pre-treatment of the H9c2 cardiac cells with NaHS or PDTC significantly suppressed the HG-induced injury, including cytotoxicity, apoptosis, oxidative stress and mitochondrial insults, as evidenced by an increase in cell viability, as well as a decrease in the number of apoptotic cells, the expression of cleaved caspase-3, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial membrane potential (MMP). In addition, pre-treatment of the cells with NaHS or PDTC ameliorated the HG-induced inflammatory response, leading to a decrease in the levels of IL-1β, IL-6 and tumor necrosis factor-α (TNF-α). Importantly, co-treatment of the H9c2 cells with 20 ng/ml IL-1 receptor antagonist (IL-1Ra) and HG markedly reduced the HG-induced increase in p-NF-κB p65 expression, cytoto xicity, the number of apoptotic cells, as well as the production of TNF-α. In conclusion, the present study presents novel mechanistic evidence that exogenous H 2 S protects H9c2 cardiac cells against HG-induced inflammation and injury, including cytotoxicity, apoptosis, overproduction of ROS and the dissipation of MMP, by inhibiting the NF-κB/IL-1β pathway. We also provide new data indicating that the positive interaction between the NF-κB pathway and IL-1β is critical in HG-induced injury and inflammation in H9c2 cardiac cells.

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Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells

Cited by 113 publications

References 37 publications

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

Ophiopogonin D Attenuates Doxorubicin-Induced Autophagic Cell Death by Relieving Mitochondrial Damage In Vitro and In Vivo

Exogenous H2S protects H9c2 cardiac cells against high glucose-induced injury and inflammation by inhibiting the activation of the NF-κB and IL-1β pathways

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