PMID- 10197541
OWN - NLM
STAT- MEDLINE
DCOM- 19990427
LR  - 20190822
IS  - 0896-6273 (Print)
IS  - 0896-6273 (Linking)
VI  - 22
IP  - 3
DP  - 1999 Mar
TI  - Caspase-8 is required for cell death induced by expanded polyglutamine repeats.
PG  - 623-33
AB  - We show here that caspase-8 is required for the death of primary rat neurons
      induced by an expanded polyglutamine repeat (Q79). Expression of Q79 recruited
      and activated caspase-8. Inhibition of caspase-8 blocked polyglutamine-induced
      cell death. Coexpression of Q79 with the caspase inhibitor CrmA, a
      dominant-negative mutant of FADD (FADD DN), Bcl-2, or Bcl-xL, but not an
      N-terminally tagged Bcl-xL, prevented the recruitment of caspase-8 and inhibited 
      polyglutamine-induced cell death. Furthermore, Western blot analysis revealed the
      presence of activated caspase-8 in the insoluble fraction of affected brain
      regions from Huntington's disease (HD) patients but not in those from
      neurologically unremarkable controls, suggesting the relocation and activation of
      caspase-8 during the pathogenesis of HD. These results suggest an essential role 
      of caspase-8 in HD-related neural degenerative diseases.
FAU - Sanchez, I
AU  - Sanchez I
AD  - Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, 
      USA.
FAU - Xu, C J
AU  - Xu CJ
FAU - Juo, P
AU  - Juo P
FAU - Kakizaka, A
AU  - Kakizaka A
FAU - Blenis, J
AU  - Blenis J
FAU - Yuan, J
AU  - Yuan J
LA  - eng
GR  - NS31862/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (FADD protein, human)
RN  - 0 (Fadd protein, rat)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Peptides)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Serpins)
RN  - 0 (Viral Proteins)
RN  - 26700-71-0 (polyglutamine)
RN  - 96282-35-8 (interleukin-1beta-converting enzyme inhibitor)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
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
CIN - Neuron. 1999 Mar;22(3):416-7. PMID: 10197520
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Carrier Proteins/biosynthesis/metabolism
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspase Inhibitors
MH  - Caspases/genetics/*physiology
MH  - Cell Line
MH  - Cysteine Proteinase Inhibitors/biosynthesis/metabolism
MH  - Enzyme Activation
MH  - Fas-Associated Death Domain Protein
MH  - Fluorescent Antibody Technique, Direct
MH  - Humans
MH  - Immunoblotting
MH  - Microscopy, Confocal
MH  - Mutation
MH  - Neurons/enzymology/*physiology
MH  - Peptides/*physiology
MH  - Plasmids
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis/metabolism
MH  - Rats
MH  - Repetitive Sequences, Amino Acid
MH  - Serpins/biosynthesis/metabolism
MH  - *Viral Proteins
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - S0896-6273(00)80716-3 [pii]
AID - 10.1016/s0896-6273(00)80716-3 [doi]
PST - ppublish
SO  - Neuron. 1999 Mar;22(3):623-33. doi: 10.1016/s0896-6273(00)80716-3.