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Abstract: PO0660

Sex Differences in Renal Mitochondrial Function of Young Healthy Rats

Session Information

  • CKD Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Schibalski, Ryan, Medical University of South Carolina, Charleston, SC, US, Charleston, South Carolina, United States
  • Sultanova, Regina F., Medical University of South Carolina, Charleston, SC, US, Charleston, United States
  • Domondon, Mark, Medical University of South Carolina, Charleston, SC, US, Charleston, South Carolina, United States
  • Mccrimmon, Allison N., Pennington Biomedical Research Center, Baton Rouge, LA, US, Baton Rouge, Louisiana, United States
  • Stadler, Krisztian, Pennington Biomedical Research Center, Baton Rouge, LA, US, Baton Rouge, Louisiana, United States
  • Ilatovskaya, Daria, Medical University of South Carolina, Charleston, SC, US, Charleston, South Carolina, United States
Background

Sex differences in mitochondrial performance have been linked to many pathologies. Premenopausal females are typically less prone to cardiorenal damage than males. Differences in the ability to manage oxidative stress, calcium uptake, fission/fusion cycles, and respiratory performance in mitochondria can affect the onset and progression of the diseases. While characteristic sex-related dissimilarities have been reported in renal function, nothing is known with regards to how sex may affect the performance of renal mitochondria. The goal of this study was to compare renal mitochondrial function in young healthy male vs female rats.

Methods

Mitochondria were isolated from the kidneys from Sprague Dawley (SD) rats (10-11 weeks). Mitochondrial membrane potential, superoxide and H2O2 levels were measured with luminescent (MCLA) or fluorescent (TMRM, Amplex Red) dyes, and seahorse analysis was performed. Antioxidant capacity was measured with a Trolox-based assay. Lipid peroxide radicals were detected using with spin resonance spectroscopy (ESR) with in vivo spin trapping.

Results

Kidneys from SD male (SDM) and female rats (SDF) were divided into cortex (SDMC, FC) and medulla (SDMM, FM). First, we report significantly higher membrane potential in SDFM compared to SDMM (p<0.001). H2O2 levels were elevated in both the SDFC and SDFM mitochondria compared to SDM (p<0.01). Interestingly, mitochondrial superoxide production was increased in the medulla compared to the cortex for both SDM and SDF, while SOD2 expression was lower (p<0.001). Antioxidant capacity was lower in SDFM tissues compared to all other groups, which is consistent with higher H2O2 level (p<0.05). Female mitochondria had significantly lower basal and ATP-linked respiration, as well as reserve and maximal capacity compared to males. In addition, we report that these parameters were lower in medullary vs cortical mitochondria, independent of sex. ESR analysis showed similar lipid peroxide radical levels in males and females, but detected a different radical adduct – an amine or amino acid-centered radical – in the medulla.

Conclusion

We report sex-related differences in mitochondrial function in the kidneys of young healthy rats. Further studies are needed to establish the mechanisms that they may affect the predisposition to kidney disease development later in life.

Funding

  • NIDDK Support –