PMID- 15659217
OWN - NLM
STAT- MEDLINE
DCOM- 20050624
LR  - 20131121
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 92
IP  - 3
DP  - 2005 Feb
TI  - Rotenone-induced caspase 9/3-independent and -dependent cell death in 
      undifferentiated and differentiated human neural stem cells.
PG  - 462-76
AB  - We used human neural stem cells (hNSCs) and their differentiated cultures as a 
      model system to evaluate the mechanism(s) involved in rotenone (RO)- and 
      camptothecin (CA)-induced cytotoxicity. Results from ultrastructural damage and 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      staining indicated that RO-induced cytotoxicity resembled CA-induced apoptosis 
      more than H(2)O(2)-induced necrosis. However, unlike CA-induced, caspase 
      9/3-dependent apoptosis, there was no increased activity in caspase 9, caspase 3 
      or poly (ADP-ribose) polymerase (PARP) cleavage in RO-induced cytotoxicity, in 
      spite of time-dependent release of cytochrome c and apoptosis-inducing factor 
      (AIF) following mitochondrial membrane depolarization and a significant increase 
      in reactive oxygen species generation. Equal doses of RO and CA used in hNSCs 
      induced caspase 9/3-dependent apoptosis in differentiated cultures. 
      Time-dependent ATP depletion occurred earlier and to a greater extent in 
      RO-treated hNSCs than in CA-treated hNSCs, or differentiated cultures treated 
      with RO or CA. In conclusion, these results represent a unique ultrastructural 
      and molecular characterization of RO- and CA-induced cytotoxicity in hNSCs and 
      their differentiated cultures. Intracellular ATP levels may play an important 
      role in determining whether neural progenitors or their differentiated cells 
      follow a caspase 9/3-dependent or -independent pathway in response to acute 
      insults from neuronal toxicants.
FAU - Li, Jiang
AU  - Li J
AD  - School of Pharmacy, University of Wisconsin at Madison, 777 Highland Avenue, 
      Madison, WI 53705-2222, USA.
FAU - Spletter, Maria L
AU  - Spletter ML
FAU - Johnson, Delinda A
AU  - Johnson DA
FAU - Wright, Lynda S
AU  - Wright LS
FAU - Svendsen, Clive N
AU  - Svendsen CN
FAU - Johnson, Jeffrey A
AU  - Johnson JA
LA  - eng
GR  - ES 08089/ES/NIEHS NIH HHS/United States
GR  - ES 10042/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Topoisomerase I Inhibitors)
RN  - 0 (Uncoupling Agents)
RN  - 03L9OT429T (Rotenone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Camptothecin/toxicity
MH  - Caspase 3
MH  - Caspase 9
MH  - Caspases/*metabolism
MH  - Cell Death/drug effects
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - DNA Fragmentation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/toxicity
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Models, Biological
MH  - Neurons/cytology/*drug effects/*enzymology
MH  - Reactive Oxygen Species/metabolism
MH  - Rotenone/*toxicity
MH  - Stem Cells/cytology/*drug effects/*enzymology
MH  - Topoisomerase I Inhibitors
MH  - Uncoupling Agents/toxicity
EDAT- 2005/01/22 09:00
MHDA- 2005/06/25 09:00
CRDT- 2005/01/22 09:00
PHST- 2005/01/22 09:00 [pubmed]
PHST- 2005/06/25 09:00 [medline]
PHST- 2005/01/22 09:00 [entrez]
AID - JNC2872 [pii]
AID - 10.1111/j.1471-4159.2004.02872.x [doi]
PST - ppublish
SO  - J Neurochem. 2005 Feb;92(3):462-76. doi: 10.1111/j.1471-4159.2004.02872.x.