An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat.

Abstract

Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) cleaves pro-IL-1 beta to produce mature IL-beta, and is a member of a family of proteases implicated in apoptosis. Intracerebroventricular (i.c.v.) administration of an irreversible ICE inhibitor, z-VAD-DCB (1 pmol, 30 min before and 15 min, 2, 4, 6 and 8 h after surgery) markedly reduced (50 +/- 4%, p < 0.001) infarct volume measured 24 h after focal cerebral ischaemia (middle cerebral artery occlusion, MCAo) in the rat. Inhibition of damage was observed in the cortex (51 +/- 5% reduction) and striatum (42 +/- 6% reduction). These data implicate ICE in ischaemic neuronal death in vivo. Inhibition of ICE could reduce ischaemic damage either by preventing IL-1 beta synthesis or by inhibiting apoptosis or by both of these processes, and may provide a useful therapeutic approach to the inhibition of ischaemic brain damage.

• Authors: S A Loddick, A MacKenzie, N J Rothwell
• Journal: Neuroreport (Neuroreport) Vol. 7 Issue 9 Pg. 1465-8 (Jun 17 1996) ISSN: 0959-4965 [Print] England
• PMID: 8856699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cysteine Proteinase Inhibitors
• Interleukin-1
• Neuroprotective Agents
• Oligopeptides
• Recombinant Proteins
• z-VAD-DCB
• Cysteine Endopeptidases
• Caspase 1

Topics

• Animals
• Caspase 1
• Cell Line
• Cells, Cultured
• Cysteine Endopeptidases (drug effects)
• Cysteine Proteinase Inhibitors (therapeutic use)
• Enzyme Activation
• Interleukin-1 (metabolism)
• Ischemic Attack, Transient (prevention & control)
• Male
• Molecular Weight
• Monocytes (drug effects, metabolism)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (therapeutic use)
• Oligopeptides (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (antagonists & inhibitors)