ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO092

Succinylation of Park 7 Activates a Protective Metabolic Response to AKI

Session Information

  • AKI: Mechanisms - III
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Pfister, Katherine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Silva Barbosa, Anne Caroline, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Chiba, Takuto, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Goetzman, Eric S., Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
  • Sims-Lucas, Sunder, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Background

Acute Kidney Injury (AKI) is extremely prevalent among hospitalizations and presents a significant risk for the development of chronic kidney disease and increased mortality. Ischemia caused by shock, trauma, and transplant are common causes of AKI. To attenuate AKI occurrence therapeutically we need a better understanding of the physiological and cellular mechanisms underlying damage. The most pronounced effect of AKI is on the Proximal Tubule Epithelial Cells (PTECs) which have the highest metabolic activity and are therefore most reliant on undisturbed blood flow and oxygen content.

Methods

We simulate AKI in vitro with hypoxia and glucose deprivation. Hypoxia signaling induces rapid posttranslational modifications (PTMs) on proteins. A growing list of PTMs have been identified and their effects described in AKI but among the understudied are succinylation and glycation.

Results

We have previously shown a protective effect on PTECs after depletion of the desuccinylase Sirtuin 5, however Sirtuin 5 is not a druggable target. Mass spectrometry analysis of Sirtuin 5 knockout PTECs revealed changes in mitochondrial and peroxisomal activity and we suggest that this activity is modulated in part by the protective effects of the deglycase Park7. Park7 expression is decreased after Ischemia-Reperfusion Injury but increased in Sirtuin 5 knockout cells.

Conclusion

These data in combination with published results of Park7’s protective role in cardiovascular damage and chronic kidney disease lead us to hypothesize that Park7 may ameliorate oxidative damage resulting from AKI and prevent disease progression. We hope to harness this mechanism to develop novel therapies for AKI.

Funding

  • NIDDK Support