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Abstract: FR-PO151

Proteomic and Functional Analysis of Acute Galactic Cosmic Radiation Exposure in the Kidneys

Session Information

  • AKI: Mechanisms - II
    November 04, 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

  • Walsh, Stephen B., University College London, London, London, United Kingdom
  • Siew, Keith, University College London, London, London, United Kingdom
Background

There is concern regarding the effect of galactic cosmic radiation (GCR) exposure on cancer risk, cardiovascular and neurological health posed by longer missions planned as part of the Deep Space Transport/Mars Missions.
However the kidney is the dose limiting organ in abdominal radiotherapy and total body irradiation. Chronic kidney dysfunction can occur with acute low linear energy transfer (LET; e.g. γ-radiation or X-rays) radiation doses as low as <0.5Gy. An astronaut on a Mars exploration mission has an estimated absorbed dose of 0.47Gy.
We hypothesise that GCR may cause acute renal failure within the timeframe and GCR dose expected for an exploratory mission to Mars, which may require renal replacement therapy and would thus be mission critical.

Methods

To investigate this, snap-frozen kidneys from mice either exposed to an acute 0.5Gy dose of simulated GCR or sham control (n=10 per group) at Brookhaven National Laboratory, underwent quantitative TMT mass spectrometry proteomic analysis for markers of proximal tubule damage and pathways known to be involved in radiation nephropathy. Urine and plasma were also collected from these mice 24hrs after acute GCR exposure for biochemical and electrolyte analysis to look for early signs of renal tubular and glomerular filtration dysfunction.

Results

Network analysis of the proteome of whole homogenised kidney of GCR exposed animals showed a biologically significant (>-10%) decrease in proteins associated with mitochondrial (e.g. CYC1, COX7C) or ribosomal function, intracellular transport and cell membrane transport (e.g. SLC12A1, SLC12A3) compared to sham exposed animals. There was a >10% increase in apolipoproteins and HDL proteins (e.g. APOA4, APOA1) in GCR compared to sham exposed animals.

Conclusion

GCR exposed animals had proteomic and biomarker evidence of renal damage. This requires further investigation.