PMID- 16528476
OWN - NLM
STAT- MEDLINE
DCOM- 20060630
LR  - 20121115
IS  - 1360-8185 (Print)
IS  - 1360-8185 (Linking)
VI  - 11
IP  - 4
DP  - 2006 Apr
TI  - N-acetylphytosphingosine-induced apoptosis of Jurkat cells is mediated by the 
      conformational change in Bak.
PG  - 581-8
AB  - N-acetylphytosphingosine (NAPS), a sphingolipid derivative, is one of the 
      well-known signal molecules that mediates various cellular functions, including 
      cell growth, differentiation, and apoptosis. In this study, we demonstrated that 
      NAPS induces apoptosis of Jurkat cells by activating Bak, but not Bax, which are 
      both members of a proapoptotic subfamily of the Bcl-2 proteins. NAPS activated 
      caspase-8 in a FADD-independent manner, but the lack of caspase-8 did not 
      suppress the activation of caspase-3 and -9 and cell death, indicating that 
      caspase-8 activation does not play an important role in NAPS-induced cell death. 
      The overexpression of Bcl-xL, an anti-apoptotic protein, completely inhibited the 
      activation of the caspases and apoptosis, assuming that NAPS-induced apoptosis 
      was initiated by the mitochondria. The expression levels of pro- and 
      anti-apoptotic Bcl-2 family members were not changed by the NAPS treatment. 
      However, Bad was translocated from the cytosol into the mitochondria, where it 
      bound to Bcl-xL, and Bak was dissociated from Bcl-xL and conformationally 
      changed. Taken together, these findings indicate that NAPS induced apoptosis of 
      Jurkat cells in a mitochondria-dependent manner that was controlled by the 
      translocation of Bad and the conformational change in Bak.
FAU - Han, Y
AU  - Han Y
AD  - Laboratory of Radiation Immunology, Korea Institute of Radiological and Medical 
      Sciences, KAERI, Gongneung-Dong, Nowon-Gu, Seoul, 139-706, Korea.
FAU - Kim, Y
AU  - Kim Y
FAU - Kang, H
AU  - Kang H
FAU - Hong, S H
AU  - Hong SH
FAU - Kim, Y H
AU  - Kim YH
FAU - Lim, D-S
AU  - Lim DS
FAU - Park, C
AU  - Park C
FAU - Yun, Y-S
AU  - Yun YS
FAU - Song, J-Y
AU  - Song JY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Sphingolipids)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-Associated Death Protein)
RN  - 0 (bcl-X Protein)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspases)
RN  - RZ4494XR10 (N-acetylphytosphingosine)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Antineoplastic Agents/*pharmacology
MH  - *Apoptosis
MH  - Caspase 8
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Fas-Associated Death Domain Protein
MH  - Humans
MH  - Jurkat Cells
MH  - Mitochondria/metabolism
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Protein Conformation
MH  - Sphingolipids/*pharmacology
MH  - bcl-2 Homologous Antagonist-Killer Protein/chemistry/*metabolism
MH  - bcl-Associated Death Protein/metabolism
MH  - bcl-X Protein/metabolism
EDAT- 2006/03/11 09:00
MHDA- 2006/07/01 09:00
CRDT- 2006/03/11 09:00
PHST- 2006/03/11 09:00 [pubmed]
PHST- 2006/07/01 09:00 [medline]
PHST- 2006/03/11 09:00 [entrez]
AID - 10.1007/s10495-006-4569-5 [doi]
PST - ppublish
SO  - Apoptosis. 2006 Apr;11(4):581-8. doi: 10.1007/s10495-006-4569-5.