BIOMAT Database Logo BIOMAT Database Logo

Inducible nitric oxide synthase induction in Thy 1 glomerulonephritis is complement and reactive oxygen species dependent. 1999

K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Department of Experimental Pathology, Imperial College School of Medicine, St. Mary's Campus, London, UK.

Thy 1 glomerulonephritis (GN) is a rat model of complement-dependent immune mesangial injury with induced glomerular nitric oxide (NO) synthesis. To examine mechanisms of inducible nitric oxide synthase (iNOS) induction, we studied the effects of treatment with the antioxidant N-acetyl-cysteine (NAC) and soluble complement receptor 1 (sCR1). Thy 1 GN was induced by intravenous anti-Thy 1 antibody. Glomeruli were isolated and kidney tissue taken from 30 min to 24 h after induction. Nitrite (NO-2) synthesis, luminol chemiluminescence for reactive oxygen species (ROS), and iNOS and cytokine mRNA were assayed in isolated glomeruli. Mesangial injury (mesangiolysis) and leucocyte infiltration were quantitated on tissue sections. NAC (i.p. 1,000 mg/kg, 1 h prior to anti-Thy 1) reduced glomerular NO-2 synthesis (3.5 +/- 0.66 vs. untreated 8.2 +/- 1.1, p = 0.02), and iNOS mRNA expression, and abolished enhanced chemiluminescence. In vitro incubation of nephritic glomeruli with 20 mM NAC also suppressed nitrite production (4.7 +/- 0.8 vs. untreated 12.2 +/- 0. 7 nmol NO-2/2,000 glomeruli/48 h, p = 0.003), and chemiluminescence. In NAC-treated animals, neutrophil infiltration (0.5 +/- 0 vs. untreated 9.6 +/- 1.6 glomerulus, p = 0.0005), and macrophage infiltration (1.7 +/- 0.4 vs. untreated 12.0 +/- 0.1, p = 0.006) were abolished, and mesangiolysis was significantly reduced (45.9 +/- 1.3 vs. untreated 34.4 +/- 2.1 cells/glomerulus, p = 0.009). NAC did not inhibit anti-Thy 1 antibody deposition. C1q was unaffected, but C3 was reduced. sCR1 treatment prevented iNOS mRNA induction, the enhanced chemiluminescence, and the neutrophil infiltration at 1 h. IL-1beta and TNFalpha mRNAs were not affected by either NAC or sCR1. These results show that NAC inhibits iNOS induction and NO synthesis in this model, and suppresses ROS synthesis and injury. They suggest that complement-dependent ROS generation is the critical initiating event that follows fixation of anti-Thy 1 antibody.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008297 Male Males
D011917 Rats, Inbred Lew An inbred strain of rat that is used in BIOMEDICAL RESEARCH. Rats, Inbred Lewis,Rats, Lew,Inbred Lew Rat,Inbred Lew Rats,Inbred Lewis Rats,Lew Rat,Lew Rat, Inbred,Lew Rats,Lew Rats, Inbred,Lewis Rats, Inbred,Rat, Inbred Lew,Rat, Lew
D011951 Receptors, Complement Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement. Complement Receptors,Complement Receptor,Complement Receptor Type 1,Receptor, Complement
D003165 Complement System Proteins Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY). Complement Proteins,Complement,Complement Protein,Hemolytic Complement,Complement, Hemolytic,Protein, Complement,Proteins, Complement,Proteins, Complement System
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D005921 Glomerulonephritis Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY. Bright Disease,Kidney Scarring,Glomerulonephritides,Scarring, Kidney
D000111 Acetylcysteine The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. Mercapturic Acid,Acemuc,Acetabs,Acetylcystein AL,Acetylcystein Atid,Acetylcystein Heumann,Acetylcystein Trom,Acetylcysteine Hydrochloride,Acetylcysteine Sodium,Acetylcysteine Zinc,Acetylcysteine, (D)-Isomer,Acetylcysteine, (DL)-Isomer,Acetylcysteine, Monoammonium Salt,Acetylcysteine, Monosodium Salt,Acetylin,Acetyst,Acétylcystéine GNR,Airbron,Alveolex,Azubronchin,Bisolvon NAC,Bromuc,Broncho-Fips,Broncholysin,Broncoclar,Codotussyl,Cystamucil,Dampo Mucopect,Eurespiran,Exomuc,Fabrol,Fluimucil,Fluprowit,Frekatuss,Genac,Hoestil,Ilube,Jenacystein,Jenapharm,Lantamed,Larylin NAC,Lindocetyl,M-Pectil,Muciteran,Muco Sanigen,Mucomyst,Mucosil,Mucosol,Mucosolvin,N-Acetyl-L-cysteine,N-Acetylcysteine,NAC AL,NAC Zambon,Optipect Hustengetränk,Siccoral,Siran,Solmucol,acebraus,durabronchal,mentopin Acetylcystein,Acetylcystein, mentopin,Acid, Mercapturic,Broncho Fips,BronchoFips,Hustengetränk, Optipect,Hydrochloride, Acetylcysteine,M Pectil,MPectil,Monoammonium Salt Acetylcysteine,Monosodium Salt Acetylcysteine,Mucopect, Dampo,N Acetyl L cysteine,N Acetylcysteine,NAC, Bisolvon,Sanigen, Muco,Sodium, Acetylcysteine,Zambon, NAC,Zinc, Acetylcysteine
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

Related Publications

K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Expression and localization of inducible nitric oxide synthase in anti-Thy-1 glomerulonephritis.
October 1995, The American journal of pathology,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Reactive oxygen species enhances the induction of inducible nitric oxide synthase by sphingomyelinase in RAW264.7 cells.
July 1998, Biochimica et biophysica acta,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Induction of inducible nitric oxide synthase increases the production of reactive oxygen species in RAW264.7 macrophages.
March 2010, Bioscience reports,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Upregulation of endothelial and inducible nitric oxide synthase expression by reactive oxygen species.
January 2008, American journal of hypertension,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Heme oxygenase-1 induction attenuates inducible nitric oxide synthase expression and proteinuria in glomerulonephritis.
December 1999, Journal of the American Society of Nephrology : JASN,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Oxygen-dependent regulation of nitric oxide production by inducible nitric oxide synthase.
December 2011, Free radical biology & medicine,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Levodopa modulating effects of inducible nitric oxide synthase and reactive oxygen species in glioma cells.
November 2002, Life sciences,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Inhibition of inducible nitric oxide synthase alters Thy-1 glomeruonephritis in rats.
January 2006, Nephron. Physiology,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Reactive oxygen and nitrogen species regulate inducible nitric oxide synthase function shifting the balance of nitric oxide and superoxide production.
February 2010, Archives of biochemistry and biophysics,
K Mosley, and S N Waddington, and H Ebrahim, and T Cook, and V Cattell
Interactions between inducible nitric oxide synthase and heme oxygenase-1 in glomerulonephritis.
March 2002, Kidney international,
Copied contents to your clipboard!