Heme oxygenase-1 localization in the rat nephron.
OBJECTIVE
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.


CONCLUSIONS
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.
Shepard
Michelle
M
Department of Medicine, Nephrology Division, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
Dhulipala
Prasad
P
Kabaria
Sunit
S
Abraham
Nader G
NG
Lianos
Elias A
EA
D000818:Animals; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis* / Q000378:metabolism; D051547:Heme Oxygenase-1; D007678:Kidney Glomerulus / Q000201:enzymology; D007685:Kidney Tubules, Collecting / Q000201:enzymology; D007686:Kidney Tubules, Distal / Q000201:enzymology; D008297:Male; D009399:Nephrons / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017971:Tin Compounds / Q000494:pharmacology
D011524:Protoporphyrins; D017971:Tin Compounds; C023599:stannous chloride; C007095:cobaltiprotoporphyrin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1