Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis
Background Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of reactive oxygen species (ROS) from podocytes may participate in the development of glomerular injury and proteinuria. We stud...
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| Format: | Article |
| Language: | English |
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The Korean Society of Nephrology
2023-03-01
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| Series: | Kidney Research and Clinical Practice |
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| Online Access: | http://krcp-ksn.org/upload/pdf/j-krcp-22-198.pdf |
| _version_ | 1827942572555763712 |
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| author | Tae-Sun Ha Su-Bin Seong Dong-Soo Ha Seung Jung Kim |
| author_facet | Tae-Sun Ha Su-Bin Seong Dong-Soo Ha Seung Jung Kim |
| author_sort | Tae-Sun Ha |
| collection | DOAJ |
| description | Background Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of reactive oxygen species (ROS) from podocytes may participate in the development of glomerular injury and proteinuria. We studied the role of oxidative stress in angiotensin II-induced podocyte apoptosis. Methods Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and were transfected with NADH/NADPH oxidase 4 (Nox4) or angiotensin II type 1 receptor for 24 hours. The changes in intracellular and mitochondrial ROS production and podocyte apoptosis were measured according to the presence of angiotensin II. Results Angiotensin II increased the generation of mitochondrial superoxide anions and ROS levels but suppressed superoxide dismutase activity in a dose- and time-dependent manner that was reversed by probucol, an antioxidant. Angiotensin II increased Nox4 protein and expression by a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of Nox4 by small interfering RNA (siRNA) reduced the oxidative stress induced by angiotensin II. Angiotensin II treatment also upregulated AT1R protein. Furthermore, angiotensin II promoted podocyte apoptosis, which was reduced significantly by probucol and Nox4 siRNA and also recovered by angiotensin II type 1 receptor siRNA. Conclusion Our findings suggest that angiotensin II increases the generation of mitochondrial superoxide anions and ROS levels via the upregulation of Nox4 and angiotensin II type 1 receptor. This can be prevented by Nox4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as use of antioxidants. |
| first_indexed | 2024-03-13T10:00:14Z |
| format | Article |
| id | doaj.art-e2550ce7b8d04d2799c533fb6794f883 |
| institution | Directory Open Access Journal |
| issn | 2211-9132 2211-9140 |
| language | English |
| last_indexed | 2024-03-13T10:00:14Z |
| publishDate | 2023-03-01 |
| publisher | The Korean Society of Nephrology |
| record_format | Article |
| series | Kidney Research and Clinical Practice |
| spelling | doaj.art-e2550ce7b8d04d2799c533fb6794f8832023-05-23T06:13:23ZengThe Korean Society of NephrologyKidney Research and Clinical Practice2211-91322211-91402023-03-0142220221510.23876/j.krcp.22.1986214Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosisTae-Sun Ha0Su-Bin Seong1Dong-Soo Ha2Seung Jung Kim3 Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Republic of Korea Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Republic of Korea Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Republic of KoreaBackground Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of reactive oxygen species (ROS) from podocytes may participate in the development of glomerular injury and proteinuria. We studied the role of oxidative stress in angiotensin II-induced podocyte apoptosis. Methods Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and were transfected with NADH/NADPH oxidase 4 (Nox4) or angiotensin II type 1 receptor for 24 hours. The changes in intracellular and mitochondrial ROS production and podocyte apoptosis were measured according to the presence of angiotensin II. Results Angiotensin II increased the generation of mitochondrial superoxide anions and ROS levels but suppressed superoxide dismutase activity in a dose- and time-dependent manner that was reversed by probucol, an antioxidant. Angiotensin II increased Nox4 protein and expression by a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of Nox4 by small interfering RNA (siRNA) reduced the oxidative stress induced by angiotensin II. Angiotensin II treatment also upregulated AT1R protein. Furthermore, angiotensin II promoted podocyte apoptosis, which was reduced significantly by probucol and Nox4 siRNA and also recovered by angiotensin II type 1 receptor siRNA. Conclusion Our findings suggest that angiotensin II increases the generation of mitochondrial superoxide anions and ROS levels via the upregulation of Nox4 and angiotensin II type 1 receptor. This can be prevented by Nox4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as use of antioxidants.http://krcp-ksn.org/upload/pdf/j-krcp-22-198.pdfangiotensin iiangiotensin type 1 receptorapoptosisnadph oxidasesoxidative stresspodocytes |
| spellingShingle | Tae-Sun Ha Su-Bin Seong Dong-Soo Ha Seung Jung Kim Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis Kidney Research and Clinical Practice angiotensin ii angiotensin type 1 receptor apoptosis nadph oxidases oxidative stress podocytes |
| title | Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis |
| title_full | Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis |
| title_fullStr | Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis |
| title_full_unstemmed | Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis |
| title_short | Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis |
| title_sort | upregulation of nadh nadph oxidase 4 by angiotensin ii induces podocyte apoptosis |
| topic | angiotensin ii angiotensin type 1 receptor apoptosis nadph oxidases oxidative stress podocytes |
| url | http://krcp-ksn.org/upload/pdf/j-krcp-22-198.pdf |
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