scholarly journals Regulatory effects of inducible nitric oxide synthase on cyclooxygenase-2 and heme oxygenase-1 expression in experimental glomerulonephritis

2005 ◽  
Vol 21 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Prasun K. Datta ◽  
Shawn Dhupar ◽  
Elias A. Lianos
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Inducible Nitric Oxide Synthase ◽  
Cyclooxygenase 2 ◽  
Heme Oxygenase 1 ◽  
Experimental Glomerulonephritis ◽  
Regulatory Effects ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Inducible nitric oxide synthase and heme oxygenase-1 in the lung during lipopolysaccharide tolerance and cross tolerance

2007 ◽  
Vol 35 (12) ◽  
pp. 2775-2784 ◽  
Author(s):  
Alexander Koch ◽  
Olaf Boehm ◽  
Paula A. Zacharowski ◽  
Stephan A. Loer ◽  
Jörg Weimann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Inducible Nitric Oxide Synthase ◽  
Heme Oxygenase 1 ◽  
Cross Tolerance ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Heme Oxygenase-1 Induction Attenuates Inducible Nitric Oxide Synthase Expression and Proteinuria in Glomerulonephritis

1999 ◽  
Vol 10 (12) ◽  
pp. 2540-2550
Author(s):  
PRASUN K. DATTA ◽  
SEVASTI B. KOUKOURITAKI ◽  
KATHLEEN A. HOPP ◽  
ELIAS A. LIANOS
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Heme Oxygenase 1 ◽  
Inos Activity ◽  
Protein Levels ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Abstract. In glomerulonephritis, there is intraglomerular activation of inducible nitric oxide synthase (iNOS) leading to high output production of nitric oxide (NO). This can result in supraphysiologic amounts of NO and cause oxidative injury. It is unknown whether mechanisms of cellular defense against NO-mediated injury exist. Induction of the heme catabolizing enzyme heme oxygenase-1 (HO-1), which generates biliverdin, carbon monoxide (CO), and iron (Fe), may provide such a mechanism, as CO and Fe are two negative modulators of iNOS activity and expression. This study assessed whether upregulation of HO-1 by a specific inducer, hemin, negatively modulates iNOS expression and activity in anti-glomerular basement membrane antibody-mediated glomerulonephritis. Glomerular HO-1 expression in nephritic animals was upregulated by treatment with hemin (30 μmol/kg body wt). iNOS and HO-1 mRNA expression were assessed by reverse transcription-PCR of glomerular total RNA from nephritic animals or nephritic animals pretreated with hemin. iNOS activity in glomeruli was measured by assessing conversion of [14C] L-arginine to [14C] L-citrulline. HO-1 protein levels in glomeruli were assessed by Western blot analysis. The effect of hemin treatment on monocyte/macrophage infiltration was assessed by enumeration of ED-1-positive cells in nephritic glomeruli. iNOS and HO-1 were coinduced in nephritic glomeruli. Hemin treatment of nephritic animals resulted in upregulation of glomerular HO-1 levels and a two- to threefold reduction in glomerular iNOS mRNA levels. iNOS activity in glomeruli was significantly reduced in hemin-treated nephritic animals in which proteinuria was also attenuated without a change in monocyte/macrophage infiltration. Hemin (100 to 200 μM) also reduced iNOS protein levels and enzyme activity in cultured mesangial cells stimulated with cytokines. These studies demonstrate that in glomerular immune injury, hemin treatment upregulates glomerular HO-1 with an attendant downregulation of iNOS expression, and thus points to regulatory interaction between the two systems. The beneficial effect of hemin treatment on proteinuria could be linked to downregulation of iNOS.

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