PMID- 15127126
OWN - NLM
STAT- MEDLINE
DCOM- 20040722
LR  - 20131121
IS  - 0371-0874 (Print)
IS  - 0371-0874 (Linking)
VI  - 56
IP  - 2
DP  - 2004 Apr 25
TI  - [The expression of Smac and XIAP in rat hippocampus following limbic seizure 
      induced by kainic acid injection into amygdaloid nucleus].
PG  - 172-7
AB  - To determine whether Smac/DIABLO (second mitochondrial activator of 
      caspases/direct inhibitor of apoptosis protein-binding protein of low isoelectric 
      point [PI]) and XIAP (X-chromosome-linked inhibitor of apoptosis protein) serve 
      to regulate neuronal apoptosis following seizures, we investigated 
      seizure-induced changes in caspase-9, Smac/DIABLO and XIAP protein expression and 
      the in vivo effect of caspase-9 inhibition. Animals received unilateral 
      intra-amygdaloid injection of kainic acid (0.5 microg) to induce seizures for 1 
      h. The seizures were then terminated by diazepam (30 mg/kg). Animals were killed 
      0, 2, 4, 8, 24 or 72 h following diazepam administration. The apoptotic and 
      surviving neurons in hippocampus were observed by terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining, 
      the expression of Smac/DIABLO, XIAP and caspase-9 was detected with 
      immunofluorescence and western blot. The results showed that the levels of XIAP 
      and the 46-kDa proenzyme form of caspase-9 were unaffected by the seizures. The 
      expression of Smac increased at 2 h and the 37-kD cleaved fragment of caspase-9 
      was detected at 4 h, TUNEL-positive neurons appeared at 8 h and reached maximal 
      at 24 h following seizure cessation within the ipsilateral (the same side as the 
      intra-amygdaloid injection of kainic acid) CA3 subfield of the hippocampus. 
      Intracerebroventricular infusion of caspase-9 inhibitor z-LEHD-fluoromethyl 
      ketone (z-LEHD-fmk) significantly decreased TUNEL-positive neurons and increased 
      the number of surviving cells. Caspase-9 immunoreactivity increased and 
      Smac/DIABLO, XIAP immunoreactivity became extensive within the ipsilateral CA3 
      neurons. TUNEL-positive neurons and the alterations of the expression of 
      Smac/DIABLO and XIAP within the ipsilateral CA3 were not detected within the 
      contralateral hippocampus. These results suggest that seizures lead the 
      translocation of Smac/DIABLO into the cytosol, the activation of caspase-9 and 
      the change of subcellular locoalization of XIAP. These changes may play a role in 
      the brain damage induced by seizures. Caspase-9 is possibly a potential 
      therapeutic target in the treatment of brain injury associated with seizures.
FAU - Li, Tian-Fu
AU  - Li TF
AD  - Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, 
      China.
FAU - Luo, Yu-Min
AU  - Luo YM
FAU - Lu, Chuan-Zhen
AU  - Lu CZ
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Sheng Li Xue Bao
JT  - Sheng li xue bao : [Acta physiologica Sinica]
JID - 20730130R
RN  - 0 (Complement Membrane Attack Complex)
RN  - 0 (Glycoproteins)
RN  - 0 (Proteins)
RN  - 0 (SC5b-9 protein complex)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 9007-36-7 (Complement System Proteins)
RN  - EC 3.4.22.- (Casp9 protein, rat)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Amygdala/*physiology
MH  - Animals
MH  - Caspase 9
MH  - Caspases/biosynthesis/genetics
MH  - Complement Membrane Attack Complex
MH  - Complement System Proteins
MH  - Glycoproteins/*biosynthesis/genetics
MH  - Hippocampus/*metabolism
MH  - Kainic Acid
MH  - Limbic System
MH  - Male
MH  - Microinjections
MH  - *Protein Biosynthesis
MH  - Proteins/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seizures/chemically induced/*metabolism
MH  - X-Linked Inhibitor of Apoptosis Protein
EDAT- 2004/05/06 05:00
MHDA- 2004/07/23 05:00
CRDT- 2004/05/06 05:00
PHST- 2004/05/06 05:00 [pubmed]
PHST- 2004/07/23 05:00 [medline]
PHST- 2004/05/06 05:00 [entrez]
PST - ppublish
SO  - Sheng Li Xue Bao. 2004 Apr 25;56(2):172-7.