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Abstract: SA-PO108

Tubular MPC1 Reduction Is a Protective Adaptive Response to Maintain Redox Balance in Rhabdomyolysis Induced 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


  • Vasquez Martinez, Gabriela, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Kim, Ji Young, The Ohio State University, Columbus, Ohio, United States
  • Mayoral Andrade, Gabriel, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Jackson, Ashley R., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Pabla, Navjot Singh P., The Ohio State University, Columbus, Ohio, United States
  • Zepeda-Orozco, Diana, Nationwide Children's Hospital, Columbus, Ohio, United States

Pyruvate is the end product of both glucose and lactate metabolism, and it is a key tubular mitochondrial metabolic fuel with important antioxidant properties that is disrupted in AKI. Pyruvate requires mitochondrial pyruvate carrier (MPC) to enter mitochondria. MPC deletion causes redox alteration characterized by disruptions in glutathione metabolism. We hypothesize tubular MPC is disrupted in AKI and has important contribution to redox responses after AKI.


Glycerol-induced rhabdomyolysis (7.5 ml/kg 50% glycerol in the hind-leg muscles) was induced in male ROSA mT/mG/Ggt1-Cre that express membrane-localized GFP in renal tubular epithelial cells, whereas all the other cell types express membrane-localized tdTomato. Kidneys were collected at 24 hours, followed by isolation of GFP positive (RTECs) and negative cells for immunoblot and gene expression analysis. Pax8Cre+/-Mpc1f/f (TMPC1-KO) mice and Pax8Cre-/-Mpc1f/f (TMPC1-WT) littermates underwent glycerol-induced rhabdomyolysis, blood and kidneys were collected at 30 hours after injury for kidney function, histology and redox response analysis.


Rhabdomyolysis induced AKI result a reduction of MPC1 mRNA and protein expression only in tubular cells. TMPC1-KO mice who underwent rhabdomyolysis induced AKI had significant reduction on serum cystatin C, blood urea nitrogen (BUN), and tubular tunel positive cells compared to WT. TMPC1-KO mice with rhabdomyolysis induced AKI had a significant increase in kidney glutathione and thioredoxin reductase activities, as well as glucose-6-phosphate dehydrogenase activity that was not significant in WT mice


Rhabdomyolysis induced AKI results on tubular MPC1 reduction. Tubular MPC1 deletion protects from rhabdomyolysis induced AKI and results on increased hydrogen peroxide antioxidant systems response capacity after injury, suggesting that MPC inhibition could be a novel therapeutic approach to manipulate redox response and protect from AKI