The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway
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...
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BMC
2020-09-01
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| Series: | BMC Microbiology |
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| Online Access: | http://link.springer.com/article/10.1186/s12866-020-01958-6 |
| _version_ | 1818289874187321344 |
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| author | Jinhua Liang Yongzhong Ning Li Dong Xiufeng Ma Shu Li Heran Yang Qi Li Ling Chen Lingjuan Gao Yanmin Xu |
| author_facet | Jinhua Liang Yongzhong Ning Li Dong Xiufeng Ma Shu Li Heran Yang Qi Li Ling Chen Lingjuan Gao Yanmin Xu |
| author_sort | Jinhua Liang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T02:19:12Z |
| format | Article |
| id | doaj.art-43b0b854b77a4d4a8e06c68e73dabf3b |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-13T02:19:12Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
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| series | BMC Microbiology |
| spelling | doaj.art-43b0b854b77a4d4a8e06c68e73dabf3b2022-12-22T00:02:49ZengBMCBMC Microbiology1471-21802020-09-0120111210.1186/s12866-020-01958-6The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathwayJinhua Liang0Yongzhong Ning1Li Dong2Xiufeng Ma3Shu Li4Heran Yang5Qi Li6Ling Chen7Lingjuan Gao8Yanmin Xu9Department of Clinical Laboratory, Hongqi Hospital Affiliated to Mudanjiang Medical UniversityDepartment of Clinical Laboratory, Beijing Chuiyangliu Hospital Affiliated to Tsinghua UniversityThree Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical CollegeThree Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical CollegeDepartment of Clinical Laboratory, Hongqi Hospital Affiliated to Mudanjiang Medical UniversityDepartment of Clinical Laboratory, Hongqi Hospital Affiliated to Mudanjiang Medical UniversityDepartment of Clinical Laboratory, Hongqi Hospital Affiliated to Mudanjiang Medical UniversityDepartment of Clinical Laboratory, Lishui District Maternal and Child Health Care CenterInstitute of translational medicine, Nanjing medical universityThree Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical CollegeAbstract 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.http://link.springer.com/article/10.1186/s12866-020-01958-6Clostridium difficileTcdAgC1qRMitochondrial function, apoptosis |
| spellingShingle | Jinhua Liang Yongzhong Ning Li Dong Xiufeng Ma Shu Li Heran Yang Qi Li Ling Chen Lingjuan Gao Yanmin Xu The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway BMC Microbiology Clostridium difficile TcdA gC1qR Mitochondrial function, apoptosis |
| title | The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway |
| title_full | The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway |
| title_fullStr | The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway |
| title_full_unstemmed | The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway |
| title_short | The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway |
| title_sort | role of the globular heads of the c1q receptor in tcda induced human colonic epithelial cell apoptosis via a mitochondria dependent pathway |
| topic | Clostridium difficile TcdA gC1qR Mitochondrial function, apoptosis |
| url | http://link.springer.com/article/10.1186/s12866-020-01958-6 |
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