PMID- 18266951
OWN - NLM
STAT- MEDLINE
DCOM- 20090402
LR  - 20211020
IS  - 1582-1838 (Print)
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Linking)
VI  - 12
IP  - 6A
DP  - 2008 Dec
TI  - Nerve growth factor blocks thapsigargin-induced apoptosis at the level of the 
      mitochondrion via regulation of Bim.
PG  - 2482-96
LID - 10.1111/j.1582-4934.2008.00268.x [doi]
AB  - This study examined how the neurotrophin, nerve growth factor (NGF), protects 
      PC12 cells against endoplasmic reticulum (ER) stress-induced apoptosis. ER stress 
      was induced using thapsigargin (TG) that inhibits the sarcoplasmic/ER Ca2+-ATPase 
      pump (SERCA) and depletes ER Ca2+ stores. NGF pre-treatment inhibited 
      translocation of Bax to the mitochondria, loss of mitochondrial transmembrane 
      potential, cytochrome c release, activation of caspases (-3, -7 and -9) and 
      apoptosis induction by TG. Notably, TG also caused a marked induction of BimEL 
      mRNA and protein, and knockdown of Bim with siRNA protected cells against 
      TG-induced apoptosis. NGF delayed the induction and increased the phosphorylation 
      of BimEL. NGF-mediated protection was dependent on phosphatidylinositol-3 kinase 
      (PI3K) signalling since all above apoptotic events, including expression and 
      phosphorylation status of BimEL protein, could be reverted by the PI3K inhibitor 
      LY294002. In contrast, NGF had no effect on the TG-mediated induction of the 
      unfolded protein response (increased expression of Grp78, GADD34, splicing of 
      XBP1 mRNA) or ER stress-associated pro-apoptotic responses (induction of C/EBP 
      homologous protein [CHOP], induction and processing of caspase-12). These data 
      indicate that NGF-mediated protection against ER stress-induced apoptosis occurs 
      at the level of the mitochondria by regulating induction and activation of Bim 
      and mitochondrial translocation of Bax.
FAU - Szegezdi, E
AU  - Szegezdi E
AD  - Department of Biochemistry, National University of Ireland, Galway, Ireland.
FAU - Herbert, K Reed
AU  - Herbert KR
FAU - Kavanagh, E T
AU  - Kavanagh ET
FAU - Samali, A
AU  - Samali A
FAU - Gorman, A M
AU  - Gorman AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080205
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Bax protein, rat)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Bcl2l11 protein, rat)
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 67526-95-8 (Thapsigargin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.4.22.- (Casp12 protein, rat)
RN  - EC 3.4.22.- (Caspase 12)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/genetics/physiology
MH  - Apoptosis Regulatory Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Base Sequence
MH  - Bcl-2-Like Protein 11
MH  - Biological Transport, Active/drug effects
MH  - Caspase 12/metabolism
MH  - DNA Primers/genetics
MH  - Endoplasmic Reticulum/drug effects/metabolism
MH  - Membrane Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Mitochondria/drug effects/metabolism
MH  - Models, Biological
MH  - Nerve Growth Factor/*pharmacology
MH  - PC12 Cells
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Folding/drug effects
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Stress, Physiological/drug effects
MH  - Thapsigargin/*antagonists & inhibitors/pharmacology
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC4514125
EDAT- 2008/02/13 09:00
MHDA- 2009/04/03 09:00
PMCR- 2008/12/01
CRDT- 2008/02/13 09:00
PHST- 2008/02/13 09:00 [pubmed]
PHST- 2009/04/03 09:00 [medline]
PHST- 2008/02/13 09:00 [entrez]
PHST- 2008/12/01 00:00 [pmc-release]
AID - JCMM268 [pii]
AID - 10.1111/j.1582-4934.2008.00268.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2008 Dec;12(6A):2482-96. doi: 10.1111/j.1582-4934.2008.00268.x. 
      Epub 2008 Feb 5.