Academic Journal
Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance
| Title: | Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance |
|---|---|
| Authors: | Tianming Qiu, Yu Zhi, Jingyuan Zhang, Ningning Wang, Xiaofeng Yao, Guang Yang, Liping Jiang, Li Lv, Xiance Sun |
| Source: | Ecotoxicology and Environmental Safety, Vol 289, Iss , Pp 117641- (2025) |
| Publisher Information: | Elsevier, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Environmental pollution LCC:Environmental sciences |
| Subject Terms: | Sodium arsenite, Islet β-cells, SET, Rac1, Cytoskeleton rearrangement, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350 |
| More Details: | Sodium arsenite (NaAsO2), the most common form of inorganic arsenic prevalent in the environment, has been closely linked to islet β-cell dysfunction, a critical pathological hallmark of type 2 diabetes (T2D). Even though apoptosis plays a pivotal role in arsenic-induced islet β-cell dysfunction, the explicit underlying mechanisms remain elusive. Here, we have identified that the SET-Rac1 signaling pathway is instrumental in the apoptosis and dysfunction of islet β-cells induced by NaAsO2. During NaAsO2-induced islet β-cell apoptosis and dysfunction, our observations indicated downregulation of SET (almost 0.5-fold) and upregulation of Rac1 (0.5-fold). Notably, overexpression of SET or inhibition of Rac1 substantially mitigated the apoptosis of islet β-cells and ameliorated the impaired insulin secretion (increased from 0.1 ng/ml to 0.2 ng/ml) caused by NaAsO2 exposure. In addition, we detected cytoskeletal disorganization following NaAsO2 treatment, characterized by elevated Cofilin-1 protein expression (approximately 2.5-fold) and disrupted cytoskeleton arrangement. Significantly, overexpression of SET or deletion of Rac1 rectified the NaAsO2-induced cytoskeletal abnormalities, as evidenced by the reduced Cofilin-1 expression and enhanced F-actin fluorescence. Our research delineates that NaAsO2 triggers apoptosis and functional impairment of islet β-cells through cytoskeletal rearrangement mediated by the SET-Rac1 pathway. This discovery could provide novel insights into therapeutic strategies for T2D provoked by environmental toxicants. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 0147-6513 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0147651324017172; https://doaj.org/toc/0147-6513 |
| DOI: | 10.1016/j.ecoenv.2024.117641 |
| Access URL: | https://doaj.org/article/33250eda6e7a46cfbb1492169d985c27 |
| Accession Number: | edsdoj.33250eda6e7a46cfbb1492169d985c27 |
| Database: | Directory of Open Access Journals |
| ISSN: | 01476513 |
|---|---|
| DOI: | 10.1016/j.ecoenv.2024.117641 |
| Published in: | Ecotoxicology and Environmental Safety |
| Language: | English |