Apocynin Attenuates Cobalt Chloride-Induced Pheochromocytoma Cell Apoptosis by Inhibiting P38-MAPK/Caspase-3 Pathway

Liu, Jie; Zhu, Yuzhang; Chen, Shipiao; Shen, Bin; Fang, Yiqun; Zhang, Yi; Shen, Ruilin

doi:10.1159/000491720

Cited by 14 publications

(8 citation statements)

References 31 publications

(32 reference statements)

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“…It has been demonstrated that CoCl 2 induces apoptosis in several types of tumour cells 12–14. To explore the effect of CoCl 2 on HCC cells, HepG2 cells were treated with different concentrations of CoCl 2 for 24 h, and then cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively.…”

Section: Resultsmentioning

confidence: 99%

<p>Cobalt Chloride Induced Apoptosis by Inhibiting GPC3 Expression via the HIF-1α/c-Myc Axis in HepG2 Cells</p>

Tong

Zhu

et al. 2019

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PurposeTo investigate the role of glypican-3 (GPC3) in cobalt chloride (CoCl2)-induced cell apoptosis in hepatocellular carcinoma.MethodsHepG2 cells were treated with CoCl2 in the absence or presence of GPC3 plasmid transfection. Cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. The expression of GPC3, hypoxia-inducible factor 1α (HIF-1α), c-myc, sp1, poly-ADP-ribose polymerase (PARP) and caspase-3 was determined by real-time PCR, Western blotting, and immunofluorescence after the cells were treated with different concentrations of CoCl2 or siRNA targeting HIF-1α.ResultsCoCl2 significantly inhibited the proliferation of HepG2 cells and induced apoptosis. Additionally, the expression of GPC3 mRNA and protein was decreased, and overexpression of GPC3 attenuated the tumour inhibiting effects. Further studies showed that CoCl2 increased the expression of HIF-1α while reducing the expression of sp1 and c-myc; knockdown of HIF-1α elevated the expression of GPC3, sp1, and c-myc.ConclusionCoCl2 inhibited the growth of HepG2 cells through downregulation of GPC3 expression via the HIF-1α/c-myc axis.

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Section: Resultsmentioning

confidence: 99%

<p>Cobalt Chloride Induced Apoptosis by Inhibiting GPC3 Expression via the HIF-1α/c-Myc Axis in HepG2 Cells</p>

Tong

Zhu

et al. 2019

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“…CoCl 2 mimics hypoxic state when applied to cell cultures [13][14][15][16][17][18][19]. Previous studies in neural-derived PC12 cells, demonstrated that CoCl 2 might induce apoptotic cell death via the P38-MAPK-caspase 3 pathway [20]. CoCl 2 interferes with heme production from protoporphyrin IX (PPIX) [19,21].…”

Section: Introductionmentioning

confidence: 99%

Efficaciousness of Low Affinity Compared to High Affinity TSPO Ligands in the Inhibition of Hypoxic Mitochondrial Cellular Damage Induced by Cobalt Chloride in Human Lung H1299 Cells

et al. 2020

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The 18 kDa translocator protein (TSPO) plays an important role in apoptotic cell death, including apoptosis induced by the hypoxia mimicking agent cobalt chloride (CoCl2). In this study, the protective effects of a high (CB86; Ki = 1.6 nM) and a low (CB204; Ki = 117.7 nM) affinity TSPO ligands were investigated in H1299 lung cancer cell line exposed to CoCl2. The lung cell line H1299 was chosen in the present study since they express TSPO and able to undergo programmed cell death. The examined cell death markers included: ATP synthase reversal, reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) depolarization, cellular toxicity, and cellular viability. Pretreatment of the cells with the low affinity ligand CB204 at a concentration of 100 µM suppressed significantly (p < 0.05 for all) CoCl2-induced cellular cytotoxicity (100%), ATP synthase reversal (67%), ROS generation (82%), Δψm depolarization (100%), reduction in cellular density (97%), and also increased cell viability (85%). Furthermore, the low affinity TSPO ligand CB204, was harmless when given by itself at 100 µM. In contrast, the high affinity ligand (CB86) was significantly effective only in the prevention of CoCl2–induced ROS generation (39%, p < 0.001), and showed significant cytotoxic effects when given alone at 100 µM, as reflected in alterations in ADP/ATP ratio, oxidative stress, mitochondrial membrane potential depolarization and cell death. It appears that similar to previous studies on brain-derived cells, the relatively low affinity for the TSPO target enhances the potency of TSPO ligands in the protection from hypoxic cell death. Moreover, the high affinity TSPO ligand CB86, but not the low affinity ligand CB204, was lethal to the lung cells at high concentration (100 µM). The low affinity TSPO ligand CB204 may be a candidate for the treatment of pulmonary diseases related to hypoxia, such as pulmonary ischemia and chronic obstructive pulmonary disease COPD.

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“…Activated p38 MAPK can inhibit Caspase-3 and Bax mRNA transcription functions via a protein-to-protein model that modulates IL-1, IL-6, IL-2, IL-8, and TNF-α and other inflammatory factors’ expression levels. [55,56] On the basis of the data in our study, p-p38 MAPK protein and apoptotic mRNAs, including Caspase-3 and Bax, were significantly increased in neutrophils following treatment with 1,25VitD3; in contrast, expression of the antiapoptosis protein Bcl-2 was decreased in the T2DM-PD-1,25VitD3 group, illustrating that the p38 MAPK signaling pathway participates in the induction of neutrophil apoptosis with 1,25VitD3. However, upon using a p38 MAPK inhibitor, neutrophil apoptosis decreased in the T2DM-SB203580 and T2DM-PD-SB203580 groups compared with that in the T2DM and T2DM-PD groups regardless of the mRNA or protein expression levels, demonstrating that the p38 MAPK pathway plays a key role in the induction of neutrophil apoptosis via 1,25VitD3.…”

Section: Discussionmentioning

confidence: 55%

1,25-dihydroxyvitamin-D3 promotes neutrophil apoptosis in periodontitis with type 2 diabetes mellitus patients via the p38/MAPK pathway

et al. 2018

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BackgroundAbnormal neutrophils are involved in many chronic endocrine diseases, including type 2 diabetes mellitus (T2DM), and in periodontitis (PD), which is a chronic inflammatory disease in which neutrophils play a vital role. The p38 mitogen-activated protein kinase (MAPK) signaling pathway participates in the apoptosis of many inflammatory cells. Additionally, 1,25-dihydroxyvitamin-D3 (1,25VitD3) as a regulator can induce responses to infection and tumor cell apoptosis. However, the effect of 1,25VitD3 in the pathogenic relationship between T2DM and PD remains unclear. The aim of this study was to assess the effect of 1,25VitD3 on neutrophil apoptosis in patients with T2DM and PD and the p38-MAPK-relevant signaling pathway mechanism in this process in vitro.MethodsNeutrophils were stained with Wright's stain, and apoptosis was detected by flow cytometry and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Apoptosis- and p38-related mRNAs and proteins were examined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and ELISA. The internal relationships were analyzed using a linear regression equation and Pearson's correlation coefficient.ResultsThe highest rate of neutrophil apoptosis occurred in cultures treated with 10–8 mol/L 1,25VitD3 in the T2DM-PD group. The apoptosis rate in the T2DM-PD-p38 inhibitor group was higher than that in the healthy control group. Western blot, ELISA and qRT-PCR results showed that the mRNA and protein expression profiles of Caspase-3 and Bax were highly up-regulated and that Bcl-2 was down-regulated in the T2DM-PD-p38 inhibitor group. The expression levels of apoptotic mRNAs and proteins in the T2DM and T2DM-PD groups were significantly higher than those in the T2DM-p38 and T2DM-PD-p38 inhibitor groups. 1,25VitD3-induced neutrophil apoptosis and phosphorylated p38 (p-p38) expression were partially inhibited by the p38 inhibitor. Expression levels of apoptosis-related genes and p-p38 in neutrophils were positively associated with increasing concentrations of 1,25VitD3. p-p38 protein expression was positively associated with the level of serum 1,25VitD3.Conclusion1,25VitD3 could promote peripheral blood neutrophil apoptosis in patients with T2DM and PD through activation of the p38-MAPK signaling pathway in vitro.

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Apocynin Attenuates Cobalt Chloride-Induced Pheochromocytoma Cell Apoptosis by Inhibiting P38-MAPK/Caspase-3 Pathway

Cited by 14 publications

References 31 publications

<p>Cobalt Chloride Induced Apoptosis by Inhibiting GPC3 Expression via the HIF-1α/c-Myc Axis in HepG2 Cells</p>

<p>Cobalt Chloride Induced Apoptosis by Inhibiting GPC3 Expression via the HIF-1α/c-Myc Axis in HepG2 Cells</p>

Efficaciousness of Low Affinity Compared to High Affinity TSPO Ligands in the Inhibition of Hypoxic Mitochondrial Cellular Damage Induced by Cobalt Chloride in Human Lung H1299 Cells

1,25-dihydroxyvitamin-D3 promotes neutrophil apoptosis in periodontitis with type 2 diabetes mellitus patients via the p38/MAPK pathway

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