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Abstract: TH-PO029

Sulfotransferase 1C2 or Its Mitochondria Membrane Product, Cholesterol Sulfate, Increases Maximum Rates of Mitochondria Redox Reactions and Utilization of Tricarboxylic Acid Intermediates

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Bacallao, Robert L., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Nagami, Glenn T., VA Greater Los Angeles Healthcare System, Los Angeles, California, United States
  • Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

In prior communications we have demonstrated that the SULT1C2 gene can induce a state of ischemia preconditioning in the kidney by increasing state II/III mitochondria respiration and membrane potential. In other studies, we have found sulfotransferase 1C2 increases state II/III mitochondria respiration when added to purified mitochondria. Thin layer chromatography studies demonstrated that sulfotransferase 1C2 converts mitochondria membrane cholesterol to cholesterol sulfate. Furthermore, adding cholesterol sulfate to purified mitochondria recapitulates the effect sulfotransferase 1C2 has on mitochondria function.

Methods

To assess the substrate specificity of carbon source utilization in S3 proximal tubule cells, we measure reduction rates of tetrazolian red in response to a supply of a single source of substrates. These studies were performed in permeabilized S3 cells with baseline measurements or following treatment with sulfotransferase 1C2 or cholesterol sulfate. OD560 was measured every 5 minutes for 12 hours at 37o C. The maximum rate of change in OD per minute was calculated from the colormetric assay .

Results

Both cholesterol sulfate or sulfotransferase 1C2 triple maximum reduction rates of tetrazolian red in response to the following substrates; cis-aconitic acid, α-keto-glutarate, succinate, fumarate, α-keto-butyrate, glutamate, glutamine, and pyruvate with 100 µM malic acid (p ≤ 0.001 for all reactions) (See accompanying graph).

Conclusion

This data demonstrates that sulfotransferase 1C2 and its mitochondria product, cholesterol-SO4 increase substrate utilization rates of tricarboxylic acid intermediates in immortalized S3 proximal tubule cells. The results show that sulfotransferase 1C2 has a novel role in cellular control of mitochondria physiology.

Substrate utilization rates in S3 cells ± sulfotransferase 1C2 treatment. Standard errors are on the order of 10E-6.

Funding

  • Veterans Affairs Support