RGD Reference Report - Oxidative stress and induction of heme oxygenase-1 in the kidney in sickle cell disease. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Oxidative stress and induction of heme oxygenase-1 in the kidney in sickle cell disease.

Authors: Nath, KA  Grande, JP  Haggard, JJ  Croatt, AJ  Katusic, ZS  Solovey, A  Hebbel, RP 
Citation: Nath KA, etal., Am J Pathol. 2001 Mar;158(3):893-903.
RGD ID: 10755563
Pubmed: PMID:11238038   (View Abstract at PubMed)
PMCID: PMC1850341   (View Article at PubMed Central)
DOI: DOI:10.1016/S0002-9440(10)64037-0   (Journal Full-text)

Chronic nephropathy is a recognized complication of sickle cell disease. Using a transgenic sickle mouse, we examined whether oxidative stress occurs in the sickle kidney, the origins and functional significance of such oxidant stress, and the expression of the oxidant-inducible, potentially protective gene, heme oxygenase-1 (HO-1); we also examined the expression of HO-1 in the kidney and in circulating endothelial cells in sickle patients. We demonstrate that this transgenic sickle mouse exhibits renal enlargement, medullary congestion, and a reduced plasma creatinine concentration. Oxidative stress is present in the kidney as indicated by increased amounts of lipid peroxidation; heme content is markedly increased in the kidney. Exacerbation of oxidative stress by inhibiting glutathione synthesis with buthionine-sulfoximine dramatically increased red blood cell sickling in the sickle kidney: in buthionine-sulfoximine-treated sickle mice, red blood cell sickling extended from the medulla into the cortical capillaries and glomeruli. HO activity is increased in the sickle mouse kidney, and is due to induction of HO-1. In the human sickle kidney, HO-1 is induced in renal tubules, interstitial cells, and in the vasculature. Expression of HO-1 is increased in circulating endothelial cells in patients with sickle cell disease. These results provide the novel demonstration that oxidative stress occurs in the sickle kidney, and that acute exacerbation of oxidative stress in the sickle mouse precipitates acute vaso-occlusive disease. Additionally, the oxidant-inducible, heme-degrading enzyme, HO-1, is induced regionally in the murine and human sickle kidney, and systemically, in circulating endothelial cells in sickle patients.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HMOX1Humansickle cell anemia  IEP  RGD 
Hmox1Ratsickle cell anemia  ISOHMOX1 (Homo sapiens) and Hmox1 (Mus musculus) RGD 
Hmox1Mousesickle cell anemia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmox1  (heme oxygenase 1)

Genes (Mus musculus)
Hmox1  (heme oxygenase 1)

Genes (Homo sapiens)
HMOX1  (heme oxygenase 1)


Additional Information