Abstract: FR-PO571
Can Acetylation of Lysine 282 of Aquaporin 3 Improve Urinary Concentration in Mice with Lithium-Induced Nephrogenic Diabetes Insipidus?
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
- Huynh, Nha V., The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Rehage, Cassidy, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Nguyen, Phi-Hung, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Hyndman, Kelly A., The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
Background
The principal cell basolateral water channel AQP3 is decreased in lithium-induced nephrogenic diabetes insipidus (NDI) and AQP3-null mice have an NDI phenotype with polyuria. We previously identified a novel AQP3 post-translational modification, acetylation of lysine 282 (K282), which we found to affect protein membrane localization. We hypothesized that lysine acetylation of AQP3 may improve the polyuria in NDI.
Methods
Mice with homozygous mutations of AQP3 K282R (deacetylated mimetic, R) or K282Q (acetylated mimetic, Q) were compared to wild type K282 (WT) mice. Male and female 11–16-week-old mice were fed a lithium-containing diet or control diet (40 mmol LiCl or NaCl/kg dry food) for 14 days (n = 5-6/group). 24 h food and water intake, urine flow, and plasma osmolality at day 14 were measured.
Results
On the control diet, food intake (WT 6.8±0.3, Q 6.3± 0.7, R 6.2±0.8 g/day, p=0.9), water intake (WT 3.6±0.3, Q 3.4±0.3, R 4.0±0.2, p=0.9), and urine flow (WT 1.4±0.4, Q 1.3±0.3, R 1.3±0.3 ml/day, p = 0.9) were similar among the male mice. The control diet females also had similar food intake (WT 6.4±0.4, Q 6.2±0.3, R 6.2±0.7 g/day, p = 0.38), water intake (WT 3.2±0.3, Q 3.4±0.2, R 3.9±0.4, p=0.9), and urine flow (WT 0.2±0.1, Q 0.5±0.1, R 0.5 ±0.2 ml/day, p=0.9). As expected, the lithium-diet fed mice developed polyuria/polydipsia. In male mice, food intake was lower in the WT (5.5±0.3 g/day) than Q and R (7.4±0.6 and 7.0±0.4 g/day, p = 0.02); however, R mutant mice had greater urine flow (12.8 ± 1.2 ml/day) than WT (4.8±0.5 ml/day) and Q mice (7.9±1.8 ml/day, p=0.0004). The females ate similar amounts of lithium diet (WT 6.4±0.3, Q 6.4±0.5, R 5.4±0.5 g/day, p=0.99) but urine flow was enhanced in Q (9.8±1.4 ml/day) and R (8.5±1.3 ml/day) mice compared to WT (4.8±0.5 ml/day, p=0.02). Water intake was significantly increased in all lithium-fed mice regardless of genotype (p<0.001). There were no significant effects of treatment or genotype on plasma osmolality among the groups.
Conclusion
Contrary to our hypothesis, AQP3 acetylation- and deacetylation-mimetics had worsened polyuria in lithium-induced NDI, suggesting that K282 is an important regulatory site for AQP3 function perhaps independent of acetylation status.
Funding
- NIDDK Support