Mechanisms of iron-induced proximal tubule injury in rat remnant kidney. 1995

D C Harris, and Y C Tay, and J Chen, and L Chen, and B J Nankivell
University of Sydney, Westmead Hospital, New South Wales, Australia.

The proposition that proximal tubule (PT) iron accumulation may cause PT injury by lysosomal destabilization or reactive oxygen species generation in human and animal chronic renal disease was examined in partially nephrectomized [remnant kidney (RK)] and sham-operated (SO) Wistar rats. Electron microscopic histochemistry with horseradish peroxidase indicated iron uptake into and release from lysosomes. PT cytoplasmic iron was seen in RK but not in SO by energy-dispersive X-ray spectrometry. Total (9.66 +/- 1.89 vs. 3.30 +/- 0.31 nmol/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 in SO. Lysosomal enzyme activity was greater in RK than in SO [e.g., N-acetyl-beta-D-glucosaminidase (NAG): 0.75 +/- 0.05 vs. 0.57 +/- 0.06 mumol p-nitrophenol.h-1.mg protein-1; P < 0.05] and was increased further by chronic iron loading (e.g., RK and NAG: 0.84 +/- 0.04 vs. 0.60 +/- 0.07; P < 0.05). There was no enzymatic 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).(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D008297 Male Males
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D009392 Nephrectomy Excision of kidney. Heminephrectomy,Heminephrectomies,Nephrectomies
D006651 Histocytochemistry Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods. Cytochemistry
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen

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