Liraglutide ameliorates COCl2-induced oxidative stress and apoptosis in H9C2 cells via regulating cell autophagy

Pang, Zhanqi; Wang, Tao; Li, Yawen; Wang, Lin; Yang, Jian; Dong, He; Li, Shijun

doi:10.3892/etm.2020.8630

Cited by 6 publications

(5 citation statements)

References 17 publications

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“…our results suggested that LRG at 100 and 1000 nmol/L for 72h promoted cell viability, whereas higher concentration of LRG (10000 nmol/L) showed signi cant toxicity to MC3T3-E1 cells. Cytotoxicity of LRG was determined by the release of lactate dehydrogenase and showed that no signi cant cytotoxicity in the 1-1000 nmol/L concentration range (Pang et al 2020). Combined with the results of mRNA expression analysis of GLP1R, pretreatment with 100nmol/L LRG for 48h was selected as the optimal condition for subsequent cell experiments, which was consistent with the research results of Sun and Wu et al (Sun et al 2020;Wu et al 2017).…”

Section: Discussionsupporting

confidence: 79%

Liraglutide attenuates palmitate-induced apoptosis via PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells

Cheng

Long

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Liraglutide (LRG), one agonist of glucagon-like peptide-1, has multiple lipid-lowering effects in type 2 diabetes mellitus, however, studies on the role of LRG in saturated fatty acid-induced bone loss are limited. Therefore, our aim was to investigate whether LRG reduces palmitate (PA)-induced apoptosis and whether the mechanism involves PKA/β-catenin/Bcl-2/Bax in osteoblastic MC3T3-E1 cells. MC3T3-E1 cells were treated with different concentrations of PA, LRG, or pretreated with Exendin 9-39 and H89, cell viability, intracellular reactive oxygen species (ROS) and cAMP levels, apoptosis and the expression of protein kinase A (PKA), β-catenin, cleaved-Capase 3, Bcl2-Associated X Protein (Bax) and B-cell lymphoma-2 (Bcl-2) along with expression of Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were evaluated. PA treatment inhibited cell proliferation and cAMP levels, elevated intracellular ROS levels and promoted apoptosis, increased protein expressions of RANKL, Bax and Cleaved-Caspase3, meanwhile decreased protein expression of OPG and Bcl-2 in a dose-dependent manner. LRG inverted PA-induced apoptosis, increased cAMP levels, promoted expression of p-PKA, p-βcatenin and reversed these gene expression via increasing GLP1R expression. Pretreatment of the cells with Exendin 9-39 and H89 partially eradicated the protective effect of LRG on PA-induced apoptosis. Therefore, these ndings indicated that LRG attenuates PA-induced apoptosis possibly by GLP1Rmediated PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-L1 cells. Our results point to LRG as a new strategy to attenuate bone loss associated with high fat diet beyond its lipid-lowering actions.

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Section: Discussionsupporting

confidence: 79%

Liraglutide attenuates palmitate-induced apoptosis via PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells

Cheng

Long

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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“…CoCl 2 is a well-known hypoxia-mimetic chemical reagent in vitro and in vivo [26,27]. Consistently, treatment with CoCl 2 at different concentrations decreased H9c2 viability and increased H9c2 apoptosis [28]. Importantly, the study revealed the significant protective effects of nesfatin-1 on CoCl 2 -induced cell injury.…”

Section: Discussionsupporting

confidence: 56%

Nesfatin-1 protects H9c2 cardiomyocytes against cobalt chloride-induced hypoxic injury by modulating the MAPK and Notch1 signaling pathways

Ren

2021

J of Biol Res-Thessaloniki

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Background This 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. Results CoCl2 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. Conclusions Nesfatin-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.

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“…ROS are an important indicators of oxidative damage and the early stage of apoptosis ( Wang et al, 2019 ; Pang et al, 2020 ). CLSM images showed that, compared with the control group, there was a significant increase in intracellular ROS under the induction of 1.4 mmol/L CoCl 2 .…”

Section: Resultsmentioning

confidence: 99%

“…Multiple studies have reported that ROS contributes to intracellular Ca 2+ overload ( Yu et al, 2014 ; Pang et al, 2020 ). Consistent with these results, ROS overproduction induced by CoCl 2 in the current study elevated the level of cytosolic Ca 2+ .…”

Section: Resultsmentioning

confidence: 99%

“…In our study, CoCl 2 increased the phosphorylation level of ERK1/2 and the apoptosis rate of HUVECs. Imbalance between the anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax (Li J. et al, 2019) can lead to opening of the mitochondrial permeability transition pore (mPTP) and consequent release of cytochrome c (Cyt-c), which then activates apoptosis effector Caspase-3 (Li X. et al, 2019;Pang et al, 2020). Our results demonstrated that pro-apoptotic protein Bax, cytoplasmic Cyt-c, and cleaved caspase-3 were significantly increased in HUVECs induced by CoCl 2 , while expression of the anti-apoptotic protein Bcl-2 protein was decreased, which collectively indicated that the mitochondrial apoptosis pathway was activated.…”

Section: Discussionmentioning

confidence: 99%

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Shenxiong glucose injection inhibits oxidative stress and apoptosis to ameliorate isoproterenol-induced myocardial ischemia in rats and improve the function of HUVECs exposed to CoCl2

Chen

et al. 2023

Front. Pharmacol.

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Background: Shenxiong Glucose Injection (SGI) is a traditional Chinese medicine formula composed of ligustrazine hydrochloride and Danshen (Radix et rhizoma Salviae miltiorrhizae; Salvia miltiorrhiza Bunge, Lamiaceae). Our previous studies and others have shown that SGI has excellent therapeutic effects on myocardial ischemia (MI). However, the potential mechanisms of action have yet to be elucidated. This study aimed to explore the molecular mechanism of SGI in MI treatment.Methods: Sprague-Dawley rats were treated with isoproterenol (ISO) to establish the MI model. Electrocardiograms, hemodynamic parameters, echocardiograms, reactive oxygen species (ROS) levels, and serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) were analyzed to explore the protective effect of SGI on MI. In addition, a model of oxidative damage and apoptosis in human umbilical vein endothelial cells (HUVECs) was established using CoCl2. Cell viability, Ca2+ concentration, mitochondrial membrane potential (MMP), apoptosis, intracellular ROS, and cell cycle parameters were detected in the HUVEC model. The expression of apoptosis-related proteins (Bcl-2, Caspase-3, PARP, cytoplasmic and mitochondrial Cyt-c and Bax, and p-ERK1/2) was determined by western blotting, and the expression of cleaved caspase-3 was analyzed by immunofluorescence.Results: SGI significantly reduced ROS production and serum concentrations of cTnI and cTnT, reversed ST-segment elevation, and attenuated the deterioration of left ventricular function in ISO-induced MI rats. In vitro, SGI treatment significantly inhibited intracellular ROS overexpression, Ca2+ influx, MMP disruption, and G2/M arrest in the cell cycle. Additionally, SGI treatment markedly upregulated the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic proteins p-ERK1/2, mitochondrial Bax, cytoplasmic Cyt-c, cleaved caspase-3, and PARP.Conclusion: SGI could improve MI by inhibiting the oxidative stress and apoptosis signaling pathways. These findings provide evidence to explain the pharmacological action and underlying molecular mechanisms of SGI in the treatment of MI.

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Liraglutide ameliorates COCl2-induced oxidative stress and apoptosis in H9C2 cells via regulating cell autophagy

Cited by 6 publications

References 17 publications

Liraglutide attenuates palmitate-induced apoptosis via PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells

Liraglutide attenuates palmitate-induced apoptosis via PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells

Nesfatin-1 protects H9c2 cardiomyocytes against cobalt chloride-induced hypoxic injury by modulating the MAPK and Notch1 signaling pathways

Shenxiong glucose injection inhibits oxidative stress and apoptosis to ameliorate isoproterenol-induced myocardial ischemia in rats and improve the function of HUVECs exposed to CoCl2

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