PMID- 17084538
OWN - NLM
STAT- MEDLINE
DCOM- 20070315
LR  - 20161124
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 144
IP  - 1
DP  - 2007 Jan 5
TI  - L-carnitine protects neurons from 1-methyl-4-phenylpyridinium-induced neuronal 
      apoptosis in rat forebrain culture.
PG  - 46-55
AB  - 1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, 
      has been widely used as a neurotoxin because it elicits a severe Parkinson's 
      disease-like syndrome with an elevation of intracellular reactive oxygen species 
      (ROS) and apoptosis. L-carnitine plays an integral role in attenuating the brain 
      injury associated with mitochondrial neurodegenerative disorders. The present 
      study investigates the effects of L-carnitine against the toxicity of MPP+ in rat 
      forebrain primary cultures. Cells in culture were treated for 24 h with 100, 250, 
      500 and 1000 microM MPP+ alone or co-incubated with L-carnitine. MPP+ produced a 
      dose-related increase in DNA fragmentation as measured by cell death ELISA 
      (enzyme-linked immunosorbent assay), an increase in the number of TUNEL (terminal 
      dUTP nick-end labeling)-positive cells and a reduction in the mitochondrial 
      metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). 
      No significant effect was observed with the release of lactate dehydrogenase 
      (LDH), indicating that cell death presumably occurred via apoptotic mechanisms. 
      Co-incubation of MPP+ with L-carnitine significantly reduced MPP+-induced 
      apoptosis. Western blot analyses showed that neurotoxic concentrations of MPP+ 
      decreased the ratio of BCL-X(L) to Bax and decreased the protein levels of 
      polysialic acid neural cell adhesion molecules (PSA-NCAM), a neuron specific 
      marker. L-carnitine blocked these effects of MPP+ suggesting its potential 
      therapeutic utility in degenerative disorders such as Parkinson's disease, 
      Alzheimer's disease, ornithine transcarbamylase deficiency and other 
      mitochondrial diseases.
FAU - Wang, C
AU  - Wang C
AD  - Division of Neurotoxicology, HFT-132, National Center for Toxicological 
      Research/U.S. Food and Drug Administration, Jefferson, AR 72079, USA. 
      cheng.wang@fda.hhs.gov
FAU - Sadovova, N
AU  - Sadovova N
FAU - Ali, H K
AU  - Ali HK
FAU - Duhart, H M
AU  - Duhart HM
FAU - Fu, X
AU  - Fu X
FAU - Zou, X
AU  - Zou X
FAU - Patterson, T A
AU  - Patterson TA
FAU - Binienda, Z K
AU  - Binienda ZK
FAU - Virmani, A
AU  - Virmani A
FAU - Paule, M G
AU  - Paule MG
FAU - Slikker, W Jr
AU  - Slikker W Jr
FAU - Ali, S F
AU  - Ali SF
LA  - eng
PT  - Journal Article
DEP - 20061102
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Sialic Acids)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (bcl-X Protein)
RN  - 0 (polysialic acid)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EUY85H477I (thiazolyl blue)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - 1-Methyl-4-phenylpyridinium/*antagonists & inhibitors/*toxicity
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Carnitine/*pharmacology
MH  - Cell Nucleus/drug effects/ultrastructure
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Neurons/*drug effects/*pathology
MH  - *Neuroprotective Agents
MH  - Prosencephalon/drug effects/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sialic Acids/metabolism
MH  - Tetrazolium Salts
MH  - Thiazoles
MH  - bcl-2-Associated X Protein/biosynthesis
MH  - bcl-X Protein/biosynthesis
EDAT- 2006/11/07 09:00
MHDA- 2007/03/16 09:00
CRDT- 2006/11/07 09:00
PHST- 2006/05/08 00:00 [received]
PHST- 2006/08/22 00:00 [revised]
PHST- 2006/08/29 00:00 [accepted]
PHST- 2006/11/07 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2006/11/07 09:00 [entrez]
AID - S0306-4522(06)01171-7 [pii]
AID - 10.1016/j.neuroscience.2006.08.083 [doi]
PST - ppublish
SO  - Neuroscience. 2007 Jan 5;144(1):46-55. doi: 10.1016/j.neuroscience.2006.08.083. 
      Epub 2006 Nov 2.