Death by a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) and protection by EGF in GH3 cells.
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.
Yoshinaga
N
N
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaidō University, Sapporo 060, Japan.
Murayama
T
T
Nomura
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D016923:Cell Death; D002999:Clone Cells / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D015259:Dopamine Agents / Q000633:toxicity*; D004815:Epidermal Growth Factor / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015259:Dopamine Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; D004815:Epidermal Growth Factor; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine