Interaction between XIAP and Smac/DIABLO in the mouse brain after transient focal cerebral ischemia.

Abstract

The X chromosome-linked inhibitor-of-apoptosis protein (XIAP) contributes to apoptosis regulation after a variety of cell death stimuli. XIAP inhibits the caspase reaction via binding to caspases, and is inhibited via binding to the second mitochondria-derived activator of caspase (Smac)/DIABLO to tightly control apoptotic cell death. However, the interaction among XIAP, Smac/DIABLO, and caspases after in vivo cerebral ischemia is not well known. To clarify this issue, the authors examined time-dependent expression and interaction among XIAP, Smac/DIABLO, and activated caspase-9 by immunohistochemistry, Western blot analysis, and immunoprecipitation using an in vivo transient focal cerebral ischemia model. To examine the relationship of the XIAP pathway to the caspase cascade, a pan-caspase inhibitor was administered. XIAP increased concurrently with the release of Smac/DIABLO and the appearance of activated caspase-9 during the early period after reperfusion injury. The bindings of XIAP to Smac/DIABLO and to caspase-9 and the binding of Smac/DIABLO to caspase-9 reached a peak simultaneously after transient focal cerebral ischemia. Neither XIAP nor Smac/DIABLO expression was affected by caspase inhibition. These results suggest that the XIAP pathway was activated upstream of the caspase cascade and that interaction among XIAP, Smac/DIABLO, and caspase-9 plays an important role in the regulation of apoptotic neuronal cell death after transient focal cerebral ischemia.

• Authors: Atsushi Saito, Takeshi Hayashi, Shuzo Okuno, Michel Ferrand-Drake, Pak H Chan
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 23 Issue 9 Pg. 1010-9 (Sep 2003) ISSN: 0271-678X [Print] United States
• PMID: 12973017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apoptosis Regulatory Proteins
• Carrier Proteins
• Cytochrome c Group
• Diablo protein, mouse
• Mitochondrial Proteins
• Proteins
• X-Linked Inhibitor of Apoptosis Protein
• Casp3 protein, mouse
• Casp9 protein, mouse
• Caspase 3
• Caspase 9
• Caspases

Topics

• Animals
• Apoptosis (physiology)
• Apoptosis Regulatory Proteins
• Brain (cytology, metabolism, pathology)
• Carrier Proteins (metabolism)
• Caspase 3
• Caspase 9
• Caspases (metabolism)
• Cytochrome c Group (metabolism)
• Enzyme Activation
• Ischemic Attack, Transient (metabolism)
• Male
• Mice
• Mitochondrial Proteins (metabolism)
• Neurons (cytology, metabolism)
• Proteins (metabolism)
• X-Linked Inhibitor of Apoptosis Protein