Abstract: TH-PO117
Acrolein Promotes Tubular Cell Death in Ischemia Reperfusion-Induced AKI
Session Information
- AKI: Mechanisms - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Aihara, Seishi, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Hirashima, Yutaro, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Torisu, Kumiko, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Kitazono, Takanari, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Nakano, Toshiaki, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Background
We previously showed that ischemia–reperfusion injury in the kidney was attenuated in arginase 2 knockout (KO) mice or arginase inhibitor-treated mice. Arginase 2 is an enzyme involved in arginine metabolism and one of its metabolites is polyamine. Polyamines, essential for cell growth and proliferation, are known to inhibit cardiovascular disease. However, under conditions of cellular damage, toxic acrolein is produced from polyamines by the enzyme spermine oxidase (SMOX).
Methods
We used a mouse renal ischemia-reperfusion model to investigate changes in the amount and localization of acrolein due to injury. We also used human proximal tubule cells (HK-2) to study whether acrolein induces renal tubular cell death. To inhibit acrolein-induced cell death, an acrolein scavenger cysteamine, or spermine oxidase (SMOX) siRNA was added to HK-2 cells. Acrolein was detected with acrolein antibody in the kidney. In HK-2 cells, acrolein was visualized with acroleinRED. To expose cells to hypoxia-reoxygenation, HK-2 cells were cultured under 1% oxygen for 24 hours, then switched to 21% oxygen for 24 hours. Mitochondrial membrane potential was determined by MitoTrackerCMXRos. Cell viability was measured by WST-8.
Results
Acrolein was accumulated in ischemia-reperfusion kidneys, particularly in tubular cells. When HK-2 cells were hypoxia-reoxygenated, acrolein accumulated and SMOX mRNA and protein levels were increased. Acrolein induced cell death and fibrosis-related TGFβ1 mRNA in HK-2 cells. Administration of cysteamine suppressed the acrolein-induced upregulation of TGFβ1 mRNA. Cysteamine also inhibited a decrease in the mitochondrial membrane potential, and cell death induced by hypoxia-reoxygenation. The siRNA-mediated knockdown of SMOX also suppressed hypoxia reoxygenation-induced acrolein accumulation and cell death.
Conclusion
Acrolein promotes tubular cell death. Accumulated acrolein in the kidney during ischemia-reperfusion injury suggested that acrolein may be directly involved in tubular cell death. Treatment to control the accumulation of acrolein might be an effective therapeutic option for renal ischemia-reperfusion injury.