Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation
Objectives Diabetic gastrointestinal dysfunction (DGD) is a serious complication of diabetic mellitus (DM), affecting the enteric nervous system (ENS), particular enteric glial cells (EGCs). This study aimed to elucidate the effects and underlying molecular mechanisms of hyperglycemic stress on EGCs...
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Taylor & Francis Group
2024-12-01
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| Series: | Redox Report |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2024.2324234 |
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| author | Yanmin Jiang Lan Xu Xue Zhu Xiaowei Zhu Xiang Xu Jianbo Li |
| author_facet | Yanmin Jiang Lan Xu Xue Zhu Xiaowei Zhu Xiang Xu Jianbo Li |
| author_sort | Yanmin Jiang |
| collection | DOAJ |
| description | Objectives Diabetic gastrointestinal dysfunction (DGD) is a serious complication of diabetic mellitus (DM), affecting the enteric nervous system (ENS), particular enteric glial cells (EGCs). This study aimed to elucidate the effects and underlying molecular mechanisms of hyperglycemic stress on EGCs in in vitro and in vivo models of DM.Methods In in vitro studies, enteric glial cell line CRL-2690 was exposed to hyperglycemia stress, and cell viability, cell apoptosis and oxidative damage were assessed. In in vivo studies, STZ-induced diabetic mice were constructed, and cell apoptosis and oxidative damage of EGCs in the duodenum of DM mice were assessed.Results The results showed that hyperglycemic stress markedly induced oxidative damage of EGCs in in vitro and in vivo models of DM. This damage was found to be dependent on the activation of redoxosomes, which involved the phosphorylation of SRC and Vav2, the up-regulation of active RAC1-GTP, and the activation of NADPH oxidase (NOX). Moreover, inhibitors of redoxosomes, such as the RAC1 inhibitor NSC23766 and the NOX inhibitor VAS2870, effectively mitigated the hyperglycemic stress-induced oxidative damage of EGCs. Additionally, inhibition of p66SHC, a downstream target of redoxosomes, attenuated oxidative damage of EGCs under hyperglycemic stress.Discussion Our findings suggest that the redoxosomes/p66SHC signaling is involved in the oxidative damage of EGCs during the pathological process of DGD. This signaling cascade may represent a potential therapeutic target for the treatment of DGD. |
| format | Article |
| id | doaj-art-1be2eb2f7cc74881bde772e6d4a26c4d |
| institution | Kabale University |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Redox Report |
| spelling | doaj-art-1be2eb2f7cc74881bde772e6d4a26c4d2024-12-07T06:20:31ZengTaylor & Francis GroupRedox Report1351-00021743-29282024-12-0129110.1080/13510002.2024.2324234Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activationYanmin Jiang0Lan Xu1Xue Zhu2Xiaowei Zhu3Xiang Xu4Jianbo Li5Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaDepartment of Endocrinology, Wuxi Medical Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Nanjing Medical University, Wuxi, People’s Republic of ChinaNational Health Commission (NHC) Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, People’s Republic of ChinaDepartment of Endocrinology, Wuxi Medical Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Nanjing Medical University, Wuxi, People’s Republic of ChinaDepartment of Endocrinology, Wuxi Medical Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Nanjing Medical University, Wuxi, People’s Republic of ChinaDepartment of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaObjectives Diabetic gastrointestinal dysfunction (DGD) is a serious complication of diabetic mellitus (DM), affecting the enteric nervous system (ENS), particular enteric glial cells (EGCs). This study aimed to elucidate the effects and underlying molecular mechanisms of hyperglycemic stress on EGCs in in vitro and in vivo models of DM.Methods In in vitro studies, enteric glial cell line CRL-2690 was exposed to hyperglycemia stress, and cell viability, cell apoptosis and oxidative damage were assessed. In in vivo studies, STZ-induced diabetic mice were constructed, and cell apoptosis and oxidative damage of EGCs in the duodenum of DM mice were assessed.Results The results showed that hyperglycemic stress markedly induced oxidative damage of EGCs in in vitro and in vivo models of DM. This damage was found to be dependent on the activation of redoxosomes, which involved the phosphorylation of SRC and Vav2, the up-regulation of active RAC1-GTP, and the activation of NADPH oxidase (NOX). Moreover, inhibitors of redoxosomes, such as the RAC1 inhibitor NSC23766 and the NOX inhibitor VAS2870, effectively mitigated the hyperglycemic stress-induced oxidative damage of EGCs. Additionally, inhibition of p66SHC, a downstream target of redoxosomes, attenuated oxidative damage of EGCs under hyperglycemic stress.Discussion Our findings suggest that the redoxosomes/p66SHC signaling is involved in the oxidative damage of EGCs during the pathological process of DGD. This signaling cascade may represent a potential therapeutic target for the treatment of DGD.https://www.tandfonline.com/doi/10.1080/13510002.2024.2324234Diabetic gastrointestinal dysfunctionenteric glial cellshyperglycemic stressredoxosomes/p66SHC signaling |
| spellingShingle | Yanmin Jiang Lan Xu Xue Zhu Xiaowei Zhu Xiang Xu Jianbo Li Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation Redox Report Diabetic gastrointestinal dysfunction enteric glial cells hyperglycemic stress redoxosomes/p66SHC signaling |
| title | Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation |
| title_full | Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation |
| title_fullStr | Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation |
| title_full_unstemmed | Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation |
| title_short | Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation |
| title_sort | hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes p66shc activation |
| topic | Diabetic gastrointestinal dysfunction enteric glial cells hyperglycemic stress redoxosomes/p66SHC signaling |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2024.2324234 |
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