PMID- 16774749
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20191210
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1098
IP  - 1
DP  - 2006 Jul 7
TI  - Inhibition of caspase-8 attenuates neuronal death induced by limbic seizures in a 
      cytochrome c-dependent and Smac/DIABLO-independent way.
PG  - 204-11
AB  - There is increasing evidence that neuronal cell death induced by seizures occurs 
      via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Caspase-8 
      cleaves Bid, which releases cytochrome c, bridging the "extrinsic" and 
      "intrinsic" pathways. Cleavage of Bid may amplify caspase-8-induced neuronal cell 
      death following seizures. In the present study, we explored the effect of an 
      inhibitor of caspase-8 (z-IETD-fmk) on the release of Smac/DIABLO and cytochrome 
      c from mitochondria. Rats received intra-amygdaloid injection of kainic acid (KA) 
      to induce seizures for 1 h. The seizures were then terminated by diazepam (30 
      mg/kg). The damaged and surviving neurons in hippocampus were observed by 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and 
      cresyl violet staining, the expression of caspase-8, Bid, XIAP, caspase-9, 
      cytochrome c and Smac/DIABLO were detected with immunofluorescence and Western 
      blot. The cleavage of caspase-8 and Bid increased at 0 h, cytosolic fraction of 
      cytochrome c and Smac/DIABLO increased by 2 h, cleavage of caspase-9 was detected 
      by 4 h, TUNEL-positive neurons appeared at 8 h and reached a maximum at 24 h 
      following administration of diazepam in the ipsilateral CA3 subfield of 
      hippocampus. Inhibition of caspase-8 significantly decreased neuronal cell death, 
      accompanied by reduction of t-Bid, cleaved caspase-9 and cytosol cytochrome c. 
      Smac/DIABLO from mitochondria was not affected. These results suggest that 
      seizures can lead the translocation of cytochrome c into the cytosol, and the 
      activation of caspase-8 occurs upstream the mitochondria release of cytochrome c 
      and Smac/DIABLO. Inhibition of caspase-8 attenuated neuronal cell death following 
      seizures by decreasing mitochondria release of cytochrome c but not Smac/DIABLO.
FAU - Li, Tianfu
AU  - Li T
AD  - Institute of Neurology, Huashan Hospital, University of Fudan, 200040 Shanghai, 
      China.
FAU - Lu, Chuanzhen
AU  - Lu C
FAU - Xia, Zuoli
AU  - Xia Z
FAU - Xiao, Baoguo
AU  - Xiao B
FAU - Luo, Yumin
AU  - Luo Y
LA  - eng
PT  - Journal Article
DEP - 20060613
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (DIABLO protein, rat)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Oligopeptides)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl 
      ketone)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.4.22.- (Casp8 protein, rat)
RN  - EC 3.4.22.- (Casp9 protein, rat)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis Regulatory Proteins
MH  - Blotting, Western
MH  - Carrier Proteins/*physiology
MH  - Caspase 8
MH  - Caspase 9
MH  - *Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cell Death/drug effects
MH  - Cytochromes c/*physiology
MH  - Cytosol/drug effects/metabolism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Functional Laterality/physiology
MH  - In Situ Nick-End Labeling
MH  - Injections, Intraventricular
MH  - Limbic System/drug effects/*physiology
MH  - Male
MH  - Mitochondrial Proteins/*physiology
MH  - Neurons/*drug effects
MH  - Oligopeptides/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seizures/enzymology
MH  - X-Linked Inhibitor of Apoptosis Protein/metabolism
EDAT- 2006/06/16 09:00
MHDA- 2006/10/25 09:00
CRDT- 2006/06/16 09:00
PHST- 2006/03/23 00:00 [received]
PHST- 2006/04/14 00:00 [revised]
PHST- 2006/04/19 00:00 [accepted]
PHST- 2006/06/16 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/06/16 09:00 [entrez]
AID - S0006-8993(06)01170-X [pii]
AID - 10.1016/j.brainres.2006.04.131 [doi]
PST - ppublish
SO  - Brain Res. 2006 Jul 7;1098(1):204-11. doi: 10.1016/j.brainres.2006.04.131. Epub 
      2006 Jun 13.