Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.14.99.3 (
heme oxygenase
)
4,196
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Complement-activation controllers, including
decay accelerating factor
(
DAF
), are gaining emphasis as they minimize injury in various dysregulated complement-activation disorders, including glomerulopathies. Heme oxygenase (HO)-1 overexpression or induction has been shown to attenuate injury in complement-dependent models of glomerulonephritis. This study investigated whether up-regulation of
DAF
by
heme oxygenase
1 (HO-1) is an underlying mechanism by using Hmox-1-deficient rats (Hmox1
+/-
; Hmox1
-/-
) or rats with HO-1 overexpression targeted to glomerular epithelial cells (GEC
HO-1
), which are particularly vulnerable to complement-mediated injury owing to their terminally differentiated nature. Constitutively expressed
DAF
was decreased in glomeruli of Hmox1
-/-
rats and augmented in glomeruli of GEC
HO-1
rats. In GEC
HO-1
rats with anti-glomerular basement membrane antibody mediated, complement-dependent injury, complement component C3 fragment b (C3b) deposition was reduced, whereas proteinuria was diminished. In glomeruli of wild-type rats, the natural Hmox substrate, hemin, induced glomerular
DAF
. This effect was attenuated in glomeruli of Hmox1
-/-
rats and augmented in glomeruli of GEC
HO-1
rats. Hemin analogues differing in either metal or porphyrin ring functionalities, acting as competitive Hmox-substrate inhibitors, also increased glomerular
DAF
and reduced C3b deposition after spontaneous complement activation. In the presence of a
DAF
-blocking antibody, the reduction in C3b deposition was reversed. These observations establish HO-1 as a physiologic regulator of glomerular
DAF
and identify hemin analogues as inducers of functional glomerular
DAF
able to minimize C3b deposition.
...
PMID:Heme Oxygenase 1 Up-Regulates Glomerular Decay Accelerating Factor Expression and Minimizes Complement Deposition and Injury. 2766 96
