X-linked inhibitor of apoptosis (XIAP) protein protects against caspase activation and tissue loss after neonatal hypoxia-ischemia

• Nine-day-old transgenic XIAP overexpressing (TG-XIAP) and wild-type mice were subjected to left carotid artery ligation and 10% O(2) for 60 min, leading to widespread infarctions in the ipsilateral hemisphere during reperfusion. The activation of caspase-3 and -9 seen in wild-type animals was virtually abolished in TG-XIAP mice. Tissue loss was significantly reduced from 54.4 +/- 4.1 mm(3) (mean +/- SEM) in wild-type mice to 33.1 +/- 2.1 mm(3) in the TG-XIAP mice. Injured neurons displayed stronger XIAP staining during reperfusion, particularly in the nuclei. XIAP was colocalized with XAF-1, Smac, and HtrA2 in injured neurons after hypoxia-ischemia (HI). XIAP was cleaved after HI, and Smac immunoprecipitation co-precipitated a 25-kDa C-terminal fragment of XIAP, indicating that Smac preferentially bound to cleaved XIAP. These findings provide the first evidence that increased XIAP levels protect the neonatal brain against HI.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Keyword

Animals

Animals

Newborn

*Apoptosis/genetics

Caspases/genetics/*metabolism

Comparative Study

Enzyme Activation/genetics

Female

Humans

Hypoxia-Ischemia

Brain/enzymology/genetics/*metabolism/*pathology

Male

Mice

Mice

Inbred C57BL

Mice

Transgenic

Protein Biosynthesis

Proteins/genetics/*physiology

Research Support

Non-U.S. Gov't

Research Support

U.S. Gov't

P.H.S.

X-Linked Inhibitor of Apoptosis Protein

Animals

Publication and Content Type

ref (subject category)

art (subject category)