PMID- 19436752
OWN - NLM
STAT- MEDLINE
DCOM- 20090807
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 5
DP  - 2009
TI  - Mitochondrial fragmentation is involved in methamphetamine-induced cell death in 
      rat hippocampal neural progenitor cells.
PG  - e5546
LID - 10.1371/journal.pone.0005546 [doi]
LID - e5546
AB  - Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of 
      dopaminergic nerve terminals and striatal cells, presumably via cross-talk 
      between the endoplasmic reticulum and mitochondria-dependent death cascades. 
      However, the effects of METH on neural progenitor cells (NPC), an important 
      reservoir for replacing neurons and glia during development and injury, remain 
      elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the 
      METH-induced mitochondrial fragmentation, apoptosis, and its related signaling 
      mechanism through immunocytochemistry, flow cytometry, and Western blotting. We 
      observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and 
      inhibited cell proliferation. The mitochondrial fission protein dynamin-related 
      protein 1 (Drp1) and reactive oxygen species (ROS), but not calcium (Ca2+) 
      influx, were involved in the regulation of METH-induced mitochondrial 
      fragmentation. Furthermore, our results indicated that dysregulation of ROS 
      contributed to the oligomerization and translocation of Drp1, resulting in 
      mitochondrial fragmentation in rhNPC. Taken together, our data demonstrate that 
      METH-mediated ROS generation results in the dysregulation of Drp1, which leads to 
      mitochondrial fragmentation and subsequent apoptosis in rhNPC. This provides a 
      potential mechanism for METH-related neurodegenerative disorders, and also 
      provides insight into therapeutic strategies for the neurodegenerative effects of 
      METH.
FAU - Tian, Changhai
AU  - Tian C
AD  - The Laboratory of Neurotoxicology at the Center for Neurovirology & 
      Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, 
      Nebraska, USA.
FAU - Murrin, L Charles
AU  - Murrin LC
FAU - Zheng, Jialin C
AU  - Zheng JC
LA  - eng
GR  - P01 NS043985/NS/NINDS NIH HHS/United States
GR  - R01 NS 061642-01/NS/NINDS NIH HHS/United States
GR  - R01 NS061642/NS/NINDS NIH HHS/United States
GR  - P20 RR15635-01/RR/NCRR NIH HHS/United States
GR  - R21 MH 083525-01/MH/NIMH NIH HHS/United States
GR  - R21 MH083525/MH/NIMH NIH HHS/United States
GR  - R01 NS041858/NS/NINDS NIH HHS/United States
GR  - P01NS043985/NS/NINDS NIH HHS/United States
GR  - P20 RR015635/RR/NCRR NIH HHS/United States
GR  - R01 NS 41858-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090514
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Dopamine Agents)
RN  - 44RAL3456C (Methamphetamine)
RN  - EC 3.6.5.5 (Dnm1l protein, rat)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cell Proliferation
MH  - Cytoplasm/metabolism
MH  - Dopamine Agents/*toxicity
MH  - Dynamins/genetics/metabolism
MH  - Fluorescent Antibody Technique
MH  - Hippocampus/*cytology/metabolism
MH  - Methamphetamine/*toxicity
MH  - Mitochondria/*drug effects/metabolism/ultrastructure
MH  - Neurons/*drug effects/metabolism
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stem Cells/cytology/*drug effects/metabolism
PMC - PMC2677674
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/05/14 09:00
MHDA- 2009/08/08 09:00
PMCR- 2009/05/14
CRDT- 2009/05/14 09:00
PHST- 2009/02/17 00:00 [received]
PHST- 2009/04/19 00:00 [accepted]
PHST- 2009/05/14 09:00 [entrez]
PHST- 2009/05/14 09:00 [pubmed]
PHST- 2009/08/08 09:00 [medline]
PHST- 2009/05/14 00:00 [pmc-release]
AID - 09-PONE-RA-08758R1 [pii]
AID - 10.1371/journal.pone.0005546 [doi]
PST - ppublish
SO  - PLoS One. 2009;4(5):e5546. doi: 10.1371/journal.pone.0005546. Epub 2009 May 14.