Abstract: SA-PO1028

Endoplasmic Reticulum Stress Induces Aminoaciduria

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 702 Water/Urea/Vasopressin, Organic Solutes

Authors

  • Koga, Moeko, Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan
  • Kato, Ayaka, Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan
  • Sonoda, Hiroko, Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan
  • Oshikawa, Sayaka, Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan
  • Ikeda, Masahiro, Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan
Background

Endoplasmic reticulum (ER) stress is caused by accumulation of misfolded proteins in the ER. ER stress is known to activate intracellular signaling pathway, named unfolded protein response (UPR). UPR has been reported to be involved in kidney disease, including acute kidney injury and diabetic nephropathy. However, the effect of ER stress on the renal physiological function is largely unknown. The purpose of this study is to clarify the effect of ER stress on the function, focusing on renal handling of amino acids.

Methods

Tunicamycin (TM), a ER stress inducer, was administered to rats by subrenal capsule injection. Urine samples were collected at 18-24 hours after injection. The composition of urinary amino acids was investigated by HPLC. Total RNA was extracted from the kidney 24 hours after administration.

Results

Real-time PCR and microarray analyses showed that GRP78 (known to be a marker for activation of the UPR) mRNA level dramatically increased in the treatment group. Urinary amino acid analysis showed that TM increased excretion of threonine, serine, glutamine, glycine, and alanine. Gene expression analyses showed that the mRNA levels of glutamine transporter (Slc38a3) and glycine transporters (Slc6a18 and Slc6a20) were significantly decreased in the TM group. Microarray analysis also showed the decrease in 7 genes out of 12 known causal genes for Fanconi syndrome.

Conclusion

These results suggest that ER stress lowers the expression levels of glutamine and glycine transporter genes, resulting in aminoaciduria. Also, it is considered that ER stress is a common mechanism of pathogenesis of aminoaciduria in Fanconi syndrome.