Abstract: FR-PO717
Angiotensin II Induces Mitochondrial Oxidative Stress in Podocyte
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1304 Glomerular Diseases: Podocyte Biology
Author
- Ha, Tae-Sun, Chungbuk National University Hospital, Cheongju, Chungcheongbuk-do, Korea (the Republic of)
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 roles of oxidative stress in angiotensin II-induced podocyte injury.
Methods
Mouse podocytes were incubated in media containing various concentrations of angiotensin II and at different incubation times and transfected by Nox4 or negative control scrambled siRNA for 24 h. The changes of the intracellular and mitochondrial ROS production were measured using respective assays and observed by confocal imaging and western blotting according to the presence of angiotensin II.
Results
Angiotensin II increased NADH/NADPH oxidase 4 protein and expression in a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of NADH/NADPH oxidase 4 by siRNA reduced the oxidative stress induced by angiotensin II. Angiotensin II also significantly increased the generation of superoxide anions and suppressed the superoxide dismutase (SOD) activity that were significantly recovered with probucol. Furthermore, angiotensin II increased the intracellular ROS levels in dose- and time-dependent manners that were also recovered with probucol.
The quantitative data of MitoSOX index demonstrated that mitochondrial superoxide production was significantly higher in angiotensin II -treated condition compared with that in untreated conditions with or without probucol at 24 h. When angiotensin II increased mitochondrial superoxide production by more than 2-fold, it was significantly recovered with probucol. We also found that cytoplasmic 8-oxo-dG immunoreactivity was significantly increased in angiotensin II -treated condition by 2-fold compared with that in untreated conditions with or without probucol at 24 h that was significantly recovered with probucol.
Conclusion
Our findings suggest that angiotensin II increased the generation of mitochondrial superoxide anions and ROS levels via the downregulation of the SOD activity and via the upregulation of NADH/NADPH oxidase 4 that were reversed by an antioxidant, probucol.
Funding
- Government Support – Non-U.S.