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Updated: Jul 30, 2026
Non-invasive Imaging of Acute Allograft Rejection after Rat Renal Transplantation Using 18F-FDG PET
Published on: April 28, 2013
Mitochondrial tyrosine nitration precedes chronic allograft nephropathy
L A MacMillan-Crow1, D L Cruthirds, K M Ahki
1Department of Surgery, UAB School of Medicine, Birmingham, AL 35294, USA. lmcrow@ccc.uab.edu
Abstract:
Endogenous tyrosine nitration and inactivation of manganese superoxide dismutase (MnSOD) has previously been reported to occur during end-stage human renal allograft rejection. In order to determine whether nitration and inactivation of this critical mitochondrial protein might play a contributory role in the onset of transplant rejection, we employed a rodent model of Chronic Allograft Nephropathy (or CAN). Using this model we followed kidney function from 2-52 weeks post-transplant and correlated graft function with levels of nitration in the renal allograft. Tyrosine nitration of both glomerular and tubular structures occurred at 2 weeks post-transplant. At later times (16 weeks) post-transplant, tyrosine nitration appeared to be confined to tubular structures; however glomerular nitration returned at 52 weeks post-transplant. Interestingly, nitration and inactivation of MnSOD occurs prior to the onset of renal dysfunction in this rat model of chronic allograft nephropathy (2 weeks versus 16 weeks post-transplant). Furthermore, we have identified an additional mitochondrial protein, cytochrome c, as being endogenously nitrated during chronic rejection. The kinetics of cytochrome c nitration lagged behind MnSOD nitration and inactivation (4 weeks compared to 2 weeks); suggesting that loss of MnSOD activity likely contributes to elevation of the nitrating species and further nitration of other targets.
Insights
Tyrosine nitration and inactivation of manganese superoxide dismutase (MnSOD) occur early in chronic allograft nephropathy (CAN) transplant rejection, preceding kidney dysfunction. This suggests MnSOD inactivation contributes to transplant rejection onset.
Area of Science:
- Immunology
- Nephrology
- Mitochondrial Biology
Background:
- Endogenous tyrosine nitration and inactivation of manganese superoxide dismutase (MnSOD) are observed in end-stage human renal allograft rejection.
- The role of MnSOD nitration and inactivation in the early stages of transplant rejection remains unclear.
Purpose of the Study:
- To investigate if nitration and inactivation of MnSOD contribute to the onset of transplant rejection.
- To examine the timeline of MnSOD nitration and inactivation relative to renal dysfunction in a rodent model of Chronic Allograft Nephropathy (CAN).
Main Methods:
- Utilized a rodent model of Chronic Allograft Nephropathy (CAN).
- Monitored kidney function from 2 to 52 weeks post-transplant.
- Correlated renal allograft function with levels of tyrosine nitration.
Main Results:
- Tyrosine nitration of glomerular and tubular structures was observed as early as 2 weeks post-transplant.
- MnSOD nitration and inactivation occurred at 2 weeks, preceding renal dysfunction at 16 weeks.
- Cytochrome c was identified as another nitrated mitochondrial protein, with nitration kinetics lagging behind MnSOD.
Conclusions:
- Early MnSOD nitration and inactivation precede renal dysfunction in CAN, suggesting a contributory role in transplant rejection.
- The findings indicate that MnSOD inactivation may lead to increased nitrating species, causing further mitochondrial damage.
- Cytochrome c is also a target of endogenous nitration during chronic rejection.
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