MITOCHONDRIAL ADAPTATION IN RENAL GROWTH &INJURY

Project: Research project

Project Details

Description

DESCRIPTION Remnant nephrons adapt to
the loss of renal mass through changes in structure and function. Some of
these compensatory adaptations appear to promote injury in these surviving
nephrons. Hemodynamic alterations have been especially emphasized as
pathways of progression. More recently they and others have focused on
several metabolic adjustments of the remnant tubule and have assessed their
potential role as mechanisms of progressive renal injury. In particular,
increased ammoniagenesis and oxygen consumption per residual nephron have
been studied and the possibility raised that complement and free radical
mediated injuries accrue to these two tubular adaptations, respectively.
Enhanced, cortical ammonia levels can trigger the complement cascade with
pro-inflammatory consequents. Increased oxygen consumption can generate
increased amounts of reactive oxygen species with cytotoxic effects.
However, their most recent studies of a model of dietary induced deficiency
of free radical scavengers, suggest that these two adaptations may be
linked. That is, augmented oxygen consumption leads to increased
generation of ammonia via the intermediary increase free radical
production. The proposed studies will provide both quantitative
descriptions of this processes at several levels and will test several
mechanistic hypotheses. Specifically, they propose to morphometrically
quantitate the proximal tubular mitochondrial compartment during adaptive
stresses since this organelle is the major site of the renal ammoniagenesis
and respiration. Second, they will measure key elements of the biochemical
machinery for these two processes in this compartment and will test the
hypothesis that ammoniagenesis is tied to respiration at least in part by
the action of reactive oxygen metabolites. Finally, they will test the
effects of manipulations of ammoniagenesis and free radical accumulation in
vivo (on renal growth and injury)."
StatusFinished
Effective start/end date8/1/917/31/96

Funding

  • National Institutes of Health: $108,256.00
  • National Institutes of Health
  • National Institutes of Health: $121,272.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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