Abstract: FR-PO575
Tamoxifen Prevents the Lithium-Induced Increased Cilium Length and Necroptosis Reduction
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Centrone, Mariangela, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
- Angelini, Ines, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
- D'Agostino, Mariagrazia, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
- Di Mise, Annarita, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
- Barile, Barbara, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
- Nicchia, Grazia Paola, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
- Tingskov, Stine Julie, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Norregaard, Rikke, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Valenti, Giovanna, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
- Tamma, Grazia, Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Bari, Italy
Background
Lithium is often used to treat some mental illnesses including bipolar disease. However, numerous adverse effects have been reported including acquired nephrogenic diabetes insipidus, a disorder characterized by a defective renal concentrating ability that causes a significant water loss. Tamoxifen, an estrogen receptor modulator, mitigates the onset of lithium-induced NDI by regulating the expression and function of AQP2 and AQP3.
Methods
Renal collecting duct MCD4 cells were used as an experimental model. Ex vivo and in vivo experiments were performed as well. Western Blotting analysis was applied to evaluate the expression and function of proteins involved in controlling cell deaths.
Results
Ex vivo and in vivo experiments revealed that treatment with Tamoxifen prevented the lithium-induced reduction in necroptosis. Specifically, Western Blotting data showed that lithium administration significantly decreased the expression levels of RIPK3 and MLKL which are key players in controlling necroptosis. Conversely, these effects were prevented by Tamoxifen treatment. In vitro experiments confirmed those findings. Also, a decrease in the expression of BID and an increase of beclin, selective markers of apoptosis and autophagy respectively, were found as well. Moreover, lithium exposure increased cell proliferation, the transepithelial electrical resistance (TEER), and the length of the primary cilium as assessed by the super-resolution stimulated emission depletion (STED) microscopy. The lithium responses were prevented by Tamoxifen treatment.
Conclusion
Together, these data revealed for the first time that exposure of renal collecting ducts to lithium resulted in a significant reduction in the expression level of selective markers of necroptosis. In addition, lithium promotes inappropriate cell proliferation possibly associated with increased transepithelial electrical resistance and elongation of the primary cilium. All these effects are prevented by Tamoxifen.
Funding
- Government Support – Non-U.S.