Abstract: TH-PO364

Oxidative Stress-Induced Intracellular Fatty Acids Imbalance Contributes to Renal Tubular Cell Damage

Session Information

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress

Authors

  • Imafuku, Tadashi, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto, Japan
  • Watanabe, Hiroshi, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto, Japan
  • Fukagawa, Masafumi, Tokai University School of Medicine, Isehara, KANAGAWA, Japan
  • Maruyama, Toru, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto, Japan
Background


Although chronic kidney disease (CKD) is one of the oxidative stress related diseases, the mechanism by which oxidative stress contributes to pathophysiology of CKD still remains unclear. Previous reports indicated that the addition of exogenous saturated fatty acid induced lipotoxicity in renal tubular cell, whereas co-incubation with unsaturated fatty acid attenuated saturated fatty acid-mediated tubular damage. However, the relationship between oxidative stress and fatty acid composition in proximal tubular cells has not been investigated.

Methods

Intracellular fatty acids composition in immortalized proximal tubule epithelial cells (HK-2 cells) was measured by GC-MS.

Results

In HK-2 cells, hydrogen peroxide treatment decreased the expression of both elongation of long chain fatty acid member 6 (Elovl6), which elongates saturated and unsaturated fatty acid with 12, 14, and 16 carbons, and stearoyl-CoA desaturase-1 (SCD1), which catalyzes the formation of monounsaturated fatty acids. At that time, intracellular unsaturated fatty acids content was significantly decreased, while cellular ER stress/apoptosis was increased. Co-treatment of anti-oxidant, N-acetylcystein recovered the reduction of Elovl6 and SCD1 expression and consequently, enhanced cellular ER stress/apoptosis were reduced. This was further confirmed by the inhibition of these enzymes using siRNA and inhibitor in which these treatments caused to the increases of cellular ER stress/apoptosis via the reduction of intracellular contents of unsaturated fatty acids. Interestingly, co-incubation with exogenous unsaturated fatty acids with siRNA for Elovl6 and inhibitor of SCD1 attenuated tubular toxicity.

Conclusion

Oxidative stress-induced intracellular fatty acids imbalance contributes to renal tubular cell damage.