Abstract: SA-PO126
Humanin, a Mitochondrial-Derived Peptide, Mitigates the Progression of Acute Kidney Disease
Session Information
- AKI: Metabolism and Cell Death
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Hsu, Yung-Ho, Taipei Medical University, Taipei, Taiwan
Background
Acute kidney disease (AKD) represents a critical period following acute kidney injury (AKI), during which preventing the onset of chronic kidney disease (CKD) becomes crucial. In this study, we investigated the impact of humanin, a mitochondrial-derived peptide, on AKD through both in vivo and in vitro experiments.
Methods
We analyzed the protective effect of humanin-G, a humanin analog, on rat renal tubular cells (NRK-52E) subjected to hypoxia/reoxygenation (H/R). We also established an AKD mouse model by performing right nephrectomy and inducing transient ischemic injury to the left kidney. One week after the operation, we administered 4 mg/Kg/week of humanin-G to AKD mice for 4 weeks.
Results
We found that H/R impaired mitochondrial function and triggered inflammatory and apoptotic responses, which were reversed by humanin treatment. Humanin treatment also reduced H/R led ROS levels. Humanin also upregulated PI3K III, downregulated phosphor-mTOR, and increased LC3 expression, all of which contribute to mitophagy. In hypoxic NRK-52E cells, humanin increased the levels of mitochondrial Complex I, which plays a crucial role in energy production within the mitochondria. Over a one-month period, humanin led to reduced serum creatinine and blood urea nitrogen levels in AKD mice. Additionally, renal fibrosis was mitigated in AKD mice treated with humanin.
Conclusion
Humanin shows promise as a potential intervention to prevent the transition from AKI to CKD. By enhancing mitochondrial function, it may play a crucial role in minimizing AKD progression.
Funding
- Government Support – Non-U.S.