Advertisement

Research Article Free access | 10.1172/JCI106697

Inducible heme oxygenase in the kidney: a model for the homeostatic control of hemoglobin catabolism

Neville R. Pimstone, Peter Engel, Raimo Tenhunen, Paul T. Seitz, Harvey S. Marver, and Rudi Schmid

Department of Medicine, University of California, San Francisco Medical Center, San Francisco, California 94122

Department of Clinical Chemistry, Meilahti Hospital, University of Helsinki, Helsinki 29, Finland

Find articles by Pimstone, N. in: PubMed | Google Scholar

Department of Medicine, University of California, San Francisco Medical Center, San Francisco, California 94122

Department of Clinical Chemistry, Meilahti Hospital, University of Helsinki, Helsinki 29, Finland

Find articles by Engel, P. in: PubMed | Google Scholar

Department of Medicine, University of California, San Francisco Medical Center, San Francisco, California 94122

Department of Clinical Chemistry, Meilahti Hospital, University of Helsinki, Helsinki 29, Finland

Find articles by Tenhunen, R. in: PubMed | Google Scholar

Department of Medicine, University of California, San Francisco Medical Center, San Francisco, California 94122

Department of Clinical Chemistry, Meilahti Hospital, University of Helsinki, Helsinki 29, Finland

Find articles by Seitz, P. in: PubMed | Google Scholar

Department of Medicine, University of California, San Francisco Medical Center, San Francisco, California 94122

Department of Clinical Chemistry, Meilahti Hospital, University of Helsinki, Helsinki 29, Finland

Find articles by Marver, H. in: PubMed | Google Scholar

Department of Medicine, University of California, San Francisco Medical Center, San Francisco, California 94122

Department of Clinical Chemistry, Meilahti Hospital, University of Helsinki, Helsinki 29, Finland

Find articles by Schmid, R. in: PubMed | Google Scholar

Published October 1, 1971 - More info

Published in Volume 50, Issue 10 on October 1, 1971
J Clin Invest. 1971;50(10):2042–2050. https://doi.org/10.1172/JCI106697.
© 1971 The American Society for Clinical Investigation
Published October 1, 1971 - Version history
View PDF
Abstract

We have recently identified and characterized NADPH-dependent microsomal heme oxygenase as the major enzymatic mechanism for the conversion of hemoglobin-heme to bilirubin-IXα in vivo. Enzyme activity is highest in tissues normally involved in red cell breakdown, that is, spleen, liver, and bone marrow, but it usually is negligible in the kidney. However, renal heme oxygenase activity may be transiently increased 30- to 100-fold following hemoglobinemia that exceeded the plasma haptoglobin-binding capacity and consequently resulted in hemoglobinuria. Maximal stimulation of enzyme activity in rats is reached 6-16 hr following a single intravenous injection of 30 mg of hemoglobin per 100 g body weight; activity returns to basal levels after about 48 hr. At peak level, total enzyme activity in the kidneys exceeds that of the spleen or liver. Cyclohexamide, puromycin, or actinomycin D, given just before, or within a few hours after, a single intravenous injection of hemoglobin minimizes or prevents the rise in renal enzyme activity; this suggests that the increase in enzyme activity is dependent on continued synthesis of ribonucleic acid and protein. The apparent biological half-life of renal heme oxygenase is about 6 hr. These observations indicate that functional adaptation of renal heme oxygenase activity reflects enzyme induction either directly or indirectly by the substrate, hemoglobin.

Filtered rather than plasma hemoglobin appears to regulate renal heme oxygenase activity. Thus, stabilization of plasma hemoglobin in its tetrameric form with bis (N-maleimidomethyl) ether, which diminishes its glomerular filtration and retards it plasma clearance, results in reduced enzyme stimulation in the kidney, but enhances its activity in the liver. These findings suggest that the enzyme is localized in the tubular epithelial cells rather than in the glomeruli and is activated by luminal hemoglobin. Direct support for this concept was obtained by the demonstration of heme oxygenase activity in renal tubules isolated from rabbits that had been injected with hemoglobin.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (October 1, 1971): No description
Advertisement
Advertisement