The Role of the Globular Heads of the C1q Receptor in TcdA-induced Human Colonic Epithelial Cell Apoptosis Via a Mitochondria-dependent Pathway

Overview

Journal BMC Microbiol

Publisher Biomed Central

Specialty Microbiology

Date 2020 Sep 4

PMID 32878596

Citations 2

Authors

Jinhua Liang

Yongzhong Ning

Li Dong

Xiufeng Ma

Shu Li

Heran Yang

Qi Li

Ling Chen

Lingjuan Gao

Yanmin Xu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer's Disease.

Guan P, Ge T, Wang P J Neuroimmune Pharmacol. 2023; 18(3):267-284.

PMID: 37386257 DOI: 10.1007/s11481-023-10076-9.

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