Clostridium difficile Toxin A Induces Reactive Oxygen Species Production and p38 MAPK Activation to Exert Cellular Toxicity in Neuronal Cells

Zhang, Peng; Hong, Ji; Yoon, I Na; Kang, Jin Ku; Hwang, Jae Sam; Kim, Ho

doi:10.4014/jmb.1702.02041

Cited by 10 publications

(19 citation statements)

References 5 publications

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“…Recent studies of epithelial cells with disruption of P38MAPK have shown that its role in cancer cells is to suppress lung, liver, and colon tumor formation in vivo [ 17 – 19 ]. Over-expression of P38MAPK has been observed in hepatocellular carcinoma, lung adenocarcinoma, colorectal carcinoma, and head and neck squamous cell carcinoma [ 20 – 22 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma

et al. 2017

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BackgroundEsophageal squamous cell carcinoma (ESCC) is a worldwide concern. This study looked at the relationship between the expression of differential proteins and the clinicopathological data and survival rate of ESCC patients to identify potential tumor markers for the growth and metastasis of ESCC.Material/MethodsThis study included 162 patients who underwent surgical excision for management of ESCC. Fresh ESCC tissue and adjacent normal tissue specimens were collected. Protein expressions were detected by western blotting. The expression of Hsp27 and P38MAPK were detected by immunohistochemistry in formalin-fixed paraffin embedded primary tissue specimens.ResultsThe rate of positive Hsp27 and P38MAPK expression in ESCC tissue were higher than in normal esophageal tissue (p<0.05). The expression of P38MAPK was related to the depth of infiltration (p<0.05). The expression of Hsp27 was correlated with lymph node metastasis (p<0.05), but not with age, depth of infiltration, or tumor size. ROC were plotted to estimate the significance of the diagnosis: for Hsp27, AUC=0.735 (p<0.05), for P38MAPK, AUC=0.882 (p<0.05).ConclusionsThe expression of Hsp27 and P38MAPK plays a role in ESCC development. Hsp27 and P38MAPK could be used as prognostic factors in ESCC.

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Section: Discussionmentioning

confidence: 99%

Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma

et al. 2017

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“…The purity of the native toxin A was assessed by gel electrophoresis, which confirmed a single protein band at the expected molecular mass of 307 kDa. Human neuroblastoma SH-SY5Y cells were maintained in MEM containing 10% FBS (Invitrogen, USA), 1% penicillin (Gibco, USA), 1% L-glutamine, 1% HEPES in a 37 o C humidified incubator with 5% CO2 [35].…”

Section: Clostridium Difficile Toxin a Preparation And Cell Culturementioning

confidence: 99%

“…SH-SY5Y cells were treated with various agents, then incubated with 3-[4,5-imethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) dye for 2 h. The solubilization reagent was added, and absorbance was determined at 570 nm by a spectrophotometer (Model 3550; Bio-Rad, Canada) [35].…”

Section: Cell Viabilitymentioning

confidence: 99%

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The Antimicrobial Peptide CopA3 Inhibits Clostridium difficile Toxin A-Induced Viability Loss and Apoptosis in Neural Cells

Yoon

Hwang

Lee

et al. 2019

Journal of Microbiology and Biotechnology

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“…The mechanisms of TcdA-induced apoptosis remain to be fully characterized. Zhang et al demonstrated that toxin A treatment results in a significant loss of viability and apoptosis in a neuronal cell line; this effect was found to depend on increased production of reactive oxygen species (ROS) and upregulation of p38 MAPK activity and p21 Cip1/Waf1 expression [16]. Carneiro et al have demonstrated that TcdA induces the cleavage of caspases 6, 8, 9, and 3 and Bid leading to human intestinal epithelial cell death [17].…”

Section: Introductionmentioning

confidence: 99%

The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway

Liang

Ning

et al. 2020

BMC Microbiol

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Background: Clostridioides (formerly Clostridium) difficile infection is the leading cause of antibiotic-associated colitis. Studies have demonstrated that C. difficile toxin A (TcdA) can cause apoptosis of many human cell types. The purpose of this study was to investigate the relationships among exposure to TcdA, the role of the receptor for the globular heads of C1q (gC1qR) gene and the underlying intracellular apoptotic mechanism in human colonic epithelial cells (NCM 460). In this study, gC1qR expression was examined using real-time polymerase chain reaction (PCR), western blotting and immunohistochemical staining. Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, and cell apoptosis was assessed by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Mitochondrial function was assessed based on reactive oxygen species (ROS) generation, changes in the mitochondrial membrane potential (ΔΨm) and the content of ATP. Results: Our study demonstrated that increasing the concentration of TcdA from 10 ng/ml to 20 ng/ml inhibited cell viability and induced cell apoptosis (p < 0.01). Moreover, the TcdA-induced gC1qR expression and enhanced expression of gC1qR caused mitochondrial dysfunction (including production of ROS and decreases in the ΔΨm and the content of ATP) and cell apoptosis. However, silencing of the gC1qR gene reversed TcdA-induced cell apoptosis and mitochondrial dysfunction. Conclusion: These data support a mechanism by which gC1qR plays a crucial role in TcdA-induced apoptosis of human colonic epithelial cells in a mitochondria-dependent manner.

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Clostridium difficile Toxin A Induces Reactive Oxygen Species Production and p38 MAPK Activation to Exert Cellular Toxicity in Neuronal Cells

Cited by 10 publications

References 5 publications

Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma

Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma

The Antimicrobial Peptide CopA3 Inhibits Clostridium difficile Toxin A-Induced Viability Loss and Apoptosis in Neural Cells

The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway

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