Mechanisms of iron-induced proximal tubule injury in the rat
remnant kidney.
Harris, David C. H., Yuet-Ching Tay, Juchuan Chen, Liguang Chen, Brian
J. Nankivell.
University of Sydney & Department Renal Medicine Westmead
Hospital, Westmead, NSW 2145, Australia, Phone: (612) 633-7388, Fax:
(612) 893-7440
APStracts 2:0048F, 1995.
The proposition that proximal tubule (PT) iron accumulation may cause
PT injury by lysosomal destabilisation or reactive oxygen species
generation in human and animal chronic renal disease was examined in
partially-nephrectomised (RK) and sham-operated (SO) Wistar rats. EM
histochemistry with horseradish peroxidase indicated iron uptake into
and release from lysosomes. PT cytoplasmic iron was seen in RK but
not SO by energy-dispersive X-ray spectrometry. Total (9.66 +/- 1.89
vs 3.30 +/- 0.31nmol/mg protein, p < 0.01), low molecular weight
(1.39 +/- 0.09 vs 0.91 +/- 0.07, p < 0.001) and catalytic iron
(1.88 +/- 0.27 vs 1.28 +/- 0.09, p = 0.05) were higher in RK
cytoplasm than SO. Lysosomal enzyme activity was greater in RK than
SO (eg. N-acetyl-[beta]-D-glucosaminidase, NAG; 0.75 +/- 0.05 vs 0.57
+/- 0.06[mu]mol pNP/hr/mg protein, p < 0.05) and was increased
further by chronic iron loading (eg. RK, NAG; 0.84 +/- 0.04 vs 0.60
+/- 0.07, p < 0.05). There was no enzymic evidence of lysosomal
fragility, and chronic iron loading of RK decreased fragility as
assessed by NAG release (1.36 +/- 0.14 vs 2.17 +/- 0.14, p < 0.05).
The lipid peroxide, malondialdehyde was increased by iron-loading in
RK cytoplasm (1.72 +/- 0.27 vs 0.81 +/- 0.14nmol/mg protein, p <
0.05) but not in the lysosomal fraction (4.60 +/- 0.69 vs 5.43 +/-
1.47, NS). In rat RK, filtered transferrin-iron is reabsorbed by
endocytosis across PT luminal membrane into lysosomes, whence
reactive iron is released to cause cytoplasmic peroxidative damage,
despite preservation of lysosomal function and stability.
Received 5 September 1994; accepted in final form 14 February
1995.
APS Manuscript Number F315-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.