Abstract: TH-PO297

RNA-Seq Analysis of Mice Exposed Acutely to Low Levels of Domoic Acid

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Grenett, Hernan E, Universiy of Alabama at Birmingham, Birmingham, Alabama, United States
  • Thompson, Robert Griffin, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • He, Lan, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Bell, P. Darwin, University of Alabama at Birmingham , Birmingham, Alabama, United States
Background

Domoic acid (DA) is produced by diatoms of the genus Pseudo-nitzschia. Exposing mammals to this glutamate analog causes a neurologic condition known as amnesic shellfish poisoning. Recently we reported that very low levels of DA (Funk, JASN 2014) are highly toxic to the kidney. DA activates ionotropic receptors in the kidney which could have multiple cellular effects on renal epithelial cells. To begin a mechanistic understanding of the renal effects of DA on kidney, we undertook RNA sequencing (RNA-Seq) studies designed to investigate how acute exposure to low levels of DA affects kidney gene expression.

Methods

Mice were injected IP with 0.05 mg/kg DA and their kidneys were harvested after 0, 15, 30, and 60 min. Total kidney RNA was isolated for RNA-Seq analysis and a sequencing library was generated using the SureSelect Stranded mRNA kit (Agilent Technologies).

Results

RNA-Seq analyses showed DA treatment affected 41 differentially-expressed-genes (DEG) that were at least 2-fold up- or down-regulated (p<0.05). In particular systems analyses indicate that genes involved in (i) lipid metabolism [Angptl4, Star], (ii) terminal cellular oxidation [Cyp11a1, Cyp11b1, Cyp21a1, Cyp24a], and (iii) plasma membrane transport [Slc22a6, Scl22a22, Slc22a26, Slc25a25] respond to DA.

Conclusion

These data reveal a complex mechanistic response by the kidney to DA. Future studies will build on and expand this intriguing preliminary data to unravel the untoward biological effects of DA.

Funding

  • Other NIH Support