Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate and the NO donor, nitroprusside, synergistically induced the death of B50 cells from a rat CNS-derived neuroblastoma cell line. With low [nitroprusside] (10 microM) both nitroprusside and glutamate were required. Under these conditions, nuclei became pyknotic and caspases were activated. The activities of caspase-3 and caspase-6 (effector caspases) were higher than those of caspase-8 and caspase-9 (initiator caspases). The activation of all four caspases was inhibited by cyclosporin A, with the order of susceptibility caspase-8=caspase-9=caspase-6>caspase-3. To identify the possible locus of cyclosporin A action, we used an antisense oligodeoxynucleotide to suppress the level of cyclophilin-A to<5% of its control value. Cyclophilin-A suppression largely reproduced the inhibitory effects of cyclosporin A. These results provide the first indication that cyclophilin-A participates in the activation of the caspase cascade in neuronal cells, in particular in the form of cascade elicited by excitotoxic stimuli. It is concluded that neuroprotection by cyclosporin A against excitotoxin-induced apoptosis is, at least partly, due to inhibition of cyclophilin-A.
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PMID:Cyclophilin-A is involved in excitotoxin-induced caspase activation in rat neuronal B50 cells. 1190 43