Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway
Objective This study aimed to investigate the therapeutic effects of sulforaphane and the role of the Nrf2-Keap1/HO-1/ROS pathway in AngII-induced oxidative stress in podocyte injury.Methods Mouse mpc5 podocytes were divided into four groups: control (Con), AngII, AngII + sulforaphane (AngII + SFN),...
Saved in:
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Renal Failure |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2416937 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849689299431194624 |
|---|---|
| author | Wen Lu |
| author_facet | Wen Lu |
| author_sort | Wen Lu |
| collection | DOAJ |
| description | Objective This study aimed to investigate the therapeutic effects of sulforaphane and the role of the Nrf2-Keap1/HO-1/ROS pathway in AngII-induced oxidative stress in podocyte injury.Methods Mouse mpc5 podocytes were divided into four groups: control (Con), AngII, AngII + sulforaphane (AngII + SFN), and control + sulforaphane (Con + SFN). Western blotting was used to detect protein expression of Nrf2-Keap1, antioxidant enzyme HO-1, and apoptosis-related proteins. ROS levels were measured using a ROS assay kit, and cell survival and viability were assayed using the CCK-8 kit. Molecular interactions between Nrf2 and sulforaphane were analyzed computationally.Results Compared with the Con group, podocytes treated with AngII alone exhibited inhibited proliferation, reduced cell viability, lower Bcl-2 expression, and higher cleaved caspase 3 expression. In the presence of sulforaphane, AngII group showed a mild inhibition on podocyte proliferation but did not induce the aforementioned changes in Bcl-2 and cleaved caspase 3 expression. Similarly, compared to the Con group, AngII treatment alone had lower Nrf2 expression and higher Keap1 expression in podocytes, accompanied by a significant decrease in ROS content. However, in the presence of sulforaphane, AngII failed to induce increases in Nrf2 and a decrease in Keap1 expression, as well as ROS levels. Furthermore, cells treated with sulforaphane exhibited higher HO-1 levels than control cells, and co-incubation with AngII did not alter HO-1 levels. Computational modeling revealed hydrophobic interactions between sulforaphane and the amino acid LYS-462 of Nrf2, as well as hydrogen bonding with amino acid HIS-465. The binding score between sulforaphane and Nrf2 was −4.7.Conclusion Sulforaphane alleviated AngII-induced podocyte oxidative stress injury via the Nrf2-Keap1/HO-1/ROS pathway, providing new insights into therapeutic compounds for mitigating chronic kidney disease. |
| format | Article |
| id | doaj-art-415f10ba671042a5966d998fadd2cb35 |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-415f10ba671042a5966d998fadd2cb352025-08-20T03:21:40ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2416937Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathwayWen Lu0Department of General Medicine, Rizhao People’s Hospital, Rizhao, ChinaObjective This study aimed to investigate the therapeutic effects of sulforaphane and the role of the Nrf2-Keap1/HO-1/ROS pathway in AngII-induced oxidative stress in podocyte injury.Methods Mouse mpc5 podocytes were divided into four groups: control (Con), AngII, AngII + sulforaphane (AngII + SFN), and control + sulforaphane (Con + SFN). Western blotting was used to detect protein expression of Nrf2-Keap1, antioxidant enzyme HO-1, and apoptosis-related proteins. ROS levels were measured using a ROS assay kit, and cell survival and viability were assayed using the CCK-8 kit. Molecular interactions between Nrf2 and sulforaphane were analyzed computationally.Results Compared with the Con group, podocytes treated with AngII alone exhibited inhibited proliferation, reduced cell viability, lower Bcl-2 expression, and higher cleaved caspase 3 expression. In the presence of sulforaphane, AngII group showed a mild inhibition on podocyte proliferation but did not induce the aforementioned changes in Bcl-2 and cleaved caspase 3 expression. Similarly, compared to the Con group, AngII treatment alone had lower Nrf2 expression and higher Keap1 expression in podocytes, accompanied by a significant decrease in ROS content. However, in the presence of sulforaphane, AngII failed to induce increases in Nrf2 and a decrease in Keap1 expression, as well as ROS levels. Furthermore, cells treated with sulforaphane exhibited higher HO-1 levels than control cells, and co-incubation with AngII did not alter HO-1 levels. Computational modeling revealed hydrophobic interactions between sulforaphane and the amino acid LYS-462 of Nrf2, as well as hydrogen bonding with amino acid HIS-465. The binding score between sulforaphane and Nrf2 was −4.7.Conclusion Sulforaphane alleviated AngII-induced podocyte oxidative stress injury via the Nrf2-Keap1/HO-1/ROS pathway, providing new insights into therapeutic compounds for mitigating chronic kidney disease.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2416937Sulforaphanepodocytesoxidative stressNrf2Keap1HO-1 |
| spellingShingle | Wen Lu Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway Renal Failure Sulforaphane podocytes oxidative stress Nrf2 Keap1 HO-1 |
| title | Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway |
| title_full | Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway |
| title_fullStr | Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway |
| title_full_unstemmed | Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway |
| title_short | Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway |
| title_sort | sulforaphane regulates angii induced podocyte oxidative stress injury through the nrf2 keap1 ho 1 ros pathway |
| topic | Sulforaphane podocytes oxidative stress Nrf2 Keap1 HO-1 |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2416937 |
| work_keys_str_mv | AT wenlu sulforaphaneregulatesangiiinducedpodocyteoxidativestressinjurythroughthenrf2keap1ho1rospathway |