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)

Programmed cell death (PCD) plays critical roles during development and in disease states. One form of programmed cell death utilizes autophagy--a cellular mechanism of degrading bulk cytosolic components--to destroy cells. Previously, the broad-spectrum caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) was shown to induce autophagic cell death. The mechanism of Zvad-induced cell death was proposed to require caspase-8 inhibition. In our report, we extend these findings to show that--as is the case for apoptosis--induction of autophagic cell death in response to zVAD results in phosphatidylserine exposure prior to loss of membrane integrity. Additionally, we show that caspase-8 inhibition is insufficient to cause autophagic cell death. Rather, the activity of a calpain-like protease must also be blocked. These results reveal the existence of an autophagic PCD-inhibiting calpain-like cysteine protease.
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PMID:A calpain-like protease inhibits autophagic cell death. 1740 99