Document Detail

Death by a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) and protection by EGF in GH3 cells.
MedLine Citation:
PMID:  9630575     Owner:  NLM     Status:  MEDLINE    
In this study we investigated the uptake and effect of a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) on a clonal strain, GH3 cells, established from rat anterior pituitary. Although the level was very low compared with that in PC12 cells, a clonal rat pheochromocytoma cell line, there was a detectable amount of tyrosine hydroxylase protein in GH3 cells. The levels of monoamines including dopamine in GH3 cells were also very low compared with those in PC12 cells. [3H]MPP+ was incorporated to GH3 cells in a concentration-dependent manner and the uptake was inhibited by nomifensine, an inhibitor of dopamine transporter. Addition of 200 microM MPP+ stimulated the leakage of lactate dehydrogenase (LDH) after a lag of 24 h. Pretreatment with 50 ng/ml of epidermal growth factor (EGF), but not nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), protected against MPP+-induced cell death. These findings show that: (1) MPP+ uptake to GH3 cells was via an effective dopamine transport system and causes delayed cell death, and (2) EGF protects against MPP+-induced cell death. A possible role for GH3 cells as dopaminergic neurons is discussed.
N Yoshinaga; T Murayama; Y Nomura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  794     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-09-02     Completed Date:  1998-09-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  137-42     Citation Subset:  IM    
Copyright Information:
Copyright 1998 Elsevier Science B.V. All rights reserved.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaidō University, Sapporo 060, Japan.
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MeSH Terms
1-Methyl-4-phenylpyridinium / toxicity*
Cell Death
Clone Cells / drug effects
Dopamine / analysis
Dopamine Agents / toxicity*
Epidermal Growth Factor / therapeutic use*
Neuroprotective Agents / therapeutic use*
Neurotoxins / toxicity*
Pituitary Gland, Anterior / cytology,  drug effects*
Tyrosine 3-Monooxygenase / analysis
Reg. No./Substance:
0/Dopamine Agents; 0/Neuroprotective Agents; 0/Neurotoxins; 48134-75-4/1-Methyl-4-phenylpyridinium; 62229-50-9/Epidermal Growth Factor; EC 3-Monooxygenase

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