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      Heme Oxygenase-1 Localization in the Rat Nephron

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          Background/Aims: Renal tubules undergo oxidative injury in various nephropathies. It is unknown whether tubular cells possess mechanisms to attenuate this form of injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, may provide such a mechanism by reducing levels of free heme, a prooxidant molecule, and by limiting activity of heme-containing prooxidant enzymes. Determination of the distribution of HO-1 in the nephron may identify those segments where HO-1 can afford protection against oxidative injury. Methods: Rats were injected subcutaneously with two different inducers of HO-1: Stannous chloride and cobalt protoporphyrin. At completion of injections, frozen sections of kidneys were stained for HO-1 using a biotin-conjugated monoclonal anti-HO-1 antibody. To identify the origin of tubules staining positive for HO-1, Tetragonolobus purpureas (TP)-derived lectin and Arachnis hypogaea (AH)-derived lectin were applied to sequential sections of the kidney cortex. Results: In rats injected with either HO-1 inducer, HO-1 was immunolocalized in tubules but not in glomeruli. Staining of sequential sections with TP-derived lectin, which binds mainly to proximal tubular cells, was negative in the tubules that stained positive for HO-1. Staining of sequential sections with AH-derived lectin, which binds mainly to distal and collecting tubular cells, was positive in those tubules that were also positive for HO-1. Conclusion: In kidneys of rats injected with inducers of HO-1, distal and collecting tubular cells were identified as the main segments of the nephron that express HO-1. We suggest that the distal nephron, by expressing HO-1, may be less vulnerable to oxidative injury.

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          Heme oxygenase: protective gene or Trojan horse.

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            Tubular atrophy in the end-stage kidney: a lectin and immunohistochemical study.

            Atrophic tubules in end-stage renal disease (ESRD) may have various morphologic appearances: some show microscopic features of "classic" atrophic tubules (thick, wrinkled tubular basement membrane and simplified epithelium), others show "thyroidization" (round tubules with simplified epithelium and casts), and many have the appearance of "endocrine" tubules (small tubules with narrow lumina, clear cells, and relatively thin basement membranes). Other tubules in ESRD may be enlarged and dilated with hypertrophic cells ("super" tubules). The exact segment of the nephron from which these tubules arise in ESRD has not been well studied. We examined paraffin sections of 28 end-stage kidneys with a panel of nephron-segment-specific renal epithelial markers (proximal nephron markers: Tetragonolobus purpureas and Phaseolus vulgaris erythroagglutinin lectins; distal nephron markers: antibodies to epithelial membrane antigen, low molecular weight cytokeratin [AE1/AE3], the lectin Arachis hypogaea, and an antibody to Tamm-Horsfall protein labeling the thick ascending limb of Henle). In addition, an antibody to proliferating cell nuclear antigen was applied to determine the proliferation index (proliferating cell nuclear antigen-positive nuclei/all counted nuclei x 100, ie, the percentage of proliferating cell nuclear antigen-positive nuclei) of the various atrophic and "super" tubules in ESRD. Classic atrophic tubules and the "super" tubules showed primarily a proximal phenotype. Tubules showing thyroidization were consistently positive with markers of the distal tubular epithelium. "Endocrine" tubules stained primarily with distal tubular markers; however, some proximal staining also was noted. The widened renal interstitium contained single cells or loosely organized small cell clusters positive with both the AE1/AE3 and the epithelial membrane antigen antibodies. Serial sectioning showed that the majority of these single cells were not forming tubules. The proliferation index of the "classic" atrophic tubules was the highest (3.08%), followed by the "super" tubules (2.39%), the "endocrine" tubules (1.58%), and the "thyroid" tubules (1.09%). These indexes are all considerably higher than the proliferation index of the normal renal tubular epithelium. Our findings suggest that different types of tubular atrophy may arise from different segments of the nephron, and that the renal interstitium in ESRD may harbor isolated cells with epithelial characteristics. Furthermore, the end-stage kidney is not a resting organ; on the contrary, it shows a high proliferative activity, particularly in the epithelium of the "classic" atrophic and the "super" tubules.

              Author and article information

              S. Karger AG
              September 2002
              26 September 2002
              : 92
              : 3
              : 660-664
              aDepartment of Medicine, Nephrology Division, Robert Wood Johnson Medical School, New Brunswick, N.J., and bDepartment of Pharmacology, New York Medical College, Valhalla, N.Y., USA
              64113 Nephron 2002;92:660–664
              © 2002 S. Karger AG, Basel

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              Page count
              Figures: 3, References: 9, Pages: 5
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              Original Paper

              Cardiovascular Medicine, Nephrology

              Tubules, Kidney, Nephron, HO-1


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