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:3.4.22.36 (
caspase-1
)
6,285
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have defined an in vitro model for the study of microvascular endothelial cell (EC) apoptosis mediated by plasma from patients with various forms of thrombotic
thrombocytopenic purpura
(
TTP
) and hemolytic-uremic syndrome (HUS). This system reproduces a variety of histopathologic and ultrastructural features of tissue EC involved in
TTP
/sporadic HUS, suggesting that apoptotic EC injury is a primary pathophysiologic event in the thrombotic microangiopathies. We now document the ability of tetrapeptide-based inhibitors of
interleukin 1beta-converting enzyme
(
ICE
)-like caspase 1 and cysteine protease protein (CPP)-32-like caspase 3, two members of a novel class of cysteine proteases involved in final pathways to apoptosis, to block
TTP
/sporadic HUS plasma-mediated apoptosis. Overexpression of Bcl-X(L) via gene transfer suppressed this apoptosis by 70%. Transduction of EC with the Bcl-2 homolog A1 had a more limited protective effect. These findings support a role for apoptosis-linked cysteine proteases in the pathophysiology of
TTP
and sporadic HUS, and raise the possibility that specific apoptosis inhibitors may have a role in the experimental therapeutics of these syndromes.
...
PMID:Role of caspases 1 and 3 and Bcl-2-related molecules in endothelial cell apoptosis associated with thrombotic microangiopathies. 984 Sep 8
