Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance
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, th...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324017172 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832590942226350080 |
|---|---|
| author | Tianming Qiu Yu Zhi Jingyuan Zhang Ningning Wang Xiaofeng Yao Guang Yang Liping Jiang Li Lv Xiance Sun |
| author_facet | Tianming Qiu Yu Zhi Jingyuan Zhang Ningning Wang Xiaofeng Yao Guang Yang Liping Jiang Li Lv Xiance Sun |
| author_sort | Tianming Qiu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-33250eda6e7a46cfbb1492169d985c27 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-33250eda6e7a46cfbb1492169d985c272025-01-23T05:25:56ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117641Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbanceTianming Qiu0Yu Zhi1Jingyuan Zhang2Ningning Wang3Xiaofeng Yao4Guang Yang5Liping Jiang6Li Lv7Xiance Sun8Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, ChinaPreventive Medicine Laboratory, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, ChinaDepartment of Pathology, the Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian 116023, China; Corresponding author.Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China; Correspondence to: Department of Occupational and Environmental Health, Global Health Research Center, School of Public Health, Dalian Medical University, Dalian 166044, China.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.http://www.sciencedirect.com/science/article/pii/S0147651324017172Sodium arseniteIslet β-cellsSETRac1Cytoskeleton rearrangement |
| spellingShingle | Tianming Qiu Yu Zhi Jingyuan Zhang Ningning Wang Xiaofeng Yao Guang Yang Liping Jiang Li Lv Xiance Sun Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance Ecotoxicology and Environmental Safety Sodium arsenite Islet β-cells SET Rac1 Cytoskeleton rearrangement |
| title | Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance |
| title_full | Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance |
| title_fullStr | Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance |
| title_full_unstemmed | Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance |
| title_short | Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance |
| title_sort | sodium arsenite induces islets β cells apoptosis and dysfunction via set rac1 mediated cytoskeleton disturbance |
| topic | Sodium arsenite Islet β-cells SET Rac1 Cytoskeleton rearrangement |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324017172 |
| work_keys_str_mv | AT tianmingqiu sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT yuzhi sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT jingyuanzhang sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT ningningwang sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT xiaofengyao sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT guangyang sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT lipingjiang sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT lilv sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance AT xiancesun sodiumarseniteinducesisletsbcellsapoptosisanddysfunctionviasetrac1mediatedcytoskeletondisturbance |