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:3.1.6.4 (
chondroitinase
)
2,039
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In the K/BxN mouse model of rheumatoid arthritis, autoantibodies specific for
glucose-6-phosphate isomerase
(
GPI
) can transfer joint-specific inflammation to most strains of normal mice. Binding of
GPI
and autoantibody to the joint surface is a prerequisite for joint-specific inflammation. However, how
GPI
localizes to the joint remains unclear. We show that glycosaminoglycans (GAGs) are the high affinity (83 nm) joint receptors for
GPI
. The binding affinity and structural differences between mouse paw/ankle GAGs and elbows/knee GAGs correlated with the distal to proximal disease severity in these joints. We found that cartilage surface
GPI
binding was greatly reduced by either
chondroitinase
ABC or beta-glucuronidase treatment. We also identified several inhibitors that inhibit both
GPI
/GAG interaction and
GPI
enzymatic activities, which suggests that the
GPI
GAG-binding domain overlaps with the active site of
GPI
enzyme. Our studies raise the possibility that GAGs are the receptors for other autoantigens involved in joint-specific inflammatory responses.
...
PMID:High affinity glycosaminoglycan and autoantigen interaction explains joint specificity in a mouse model of rheumatoid arthritis. 1894 58
