Abstract
BackgroundThis study aimed to explore the effect of nesfatin-1 on cobalt chloride (CoCl2)-induced hypoxic injury in cardiomyocyte H9c2 cells.Methods H9c2 cardiomyocytes were induced by different concentrations of CoCl2 to mimic the hypoxia condition. Cell viability was detected by MTT assay. Cell apoptosis was detected by TUNEL staining and flow cytometry. ROS production was detected using the fluorescence probe DCFH-DA. The mitochondrial membrane potential (MMP) was detected using the TMRE method. The levels of released lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were detected using the commercial kits. The protein levels of MAPK signaling members (p-JNK1/2, p-ERK1/2, and p-p38) and Notch1 signaling members (Notch1, Hes 1, and Jagged 1) were detected by Western blot.ResultsCoCl2 significantly promoted cell apoptosis, increased LDH leakage, MDA concentration, and decreased cell viability, SOD activity, GSH production, and CAT activity. CoCl2-induced hypoxic injury in H9c2 cells was partially restored by nesfatin-1 treatment. Moreover, nesfatin-1 treatment attenuated CoCl2-induced increase in ROS production and mitochondrial dysfunction, decreased mitochondrial membrane potential, Bax/Bcl-2 imbalance, as well as c-caspase-9 and c-caspase-3 levels. Moreover, nesfatin-1 treatment inhibited the activation of MAPK and Notch1 signaling pathways.ConclusionsNesfatin-1 could effectively protect H9c2 cells against CoCl2-induced hypoxic injury by blocking MAPK and Notch1 signaling pathways, suggesting that nesfatin-1 might be a promising therapeutic agent for hypoxic cardiac injury.
Highlights
This study aimed to explore the effect of nesfatin-1 on cobalt chloride (CoCl2)-induced hypoxic injury in cardiomyocyte H9c2 cells
CoCl2 inhibited proliferation, induced apoptosis, and activated mitogen-activated protein kinase (MAPK) and Notch1 signaling pathways in H9c2 cells To confirm the toxicity of CoCl2 in H9c2 cells, H9c2 cells were treated with different concentrations of CoCl2 for 24 or 48 h
These results suggested that C oCl2 could significantly inhibit proliferation, induce apoptosis, and activate MAPK and Notch1 signaling pathways in H9c2 cells
Summary
This study aimed to explore the effect of nesfatin-1 on cobalt chloride (CoCl2)-induced hypoxic injury in cardiomyocyte H9c2 cells. MAPK signaling pathway has been identified to be associated with cardiomyocyte apoptosis triggered by ROS [9]. Another signaling pathway triggered by ROS is the Notch pathway, and activation of the Notch pathway can induce downstream proteins involved in the cell cycle and apoptosis, including Notch, Hes-1, Hes-5, and Jagged1 [10, 11]. These reports indicate that targeting MAPK and Notch signaling pathways may be a potential treatment to prevent ROS-induced cardiomyocyte injury
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