Brain-derived and glial cell line-derived neurotrophic factors protect a catecholaminergic cell line from dopamine-induced cell death.
Brain-derived neurotrophic factor (BDNF) promotes the survival of dopaminergic neurons in primary cultures and protects these neurons from the neurotoxic effects of 6-hydroxydopamine. The protective mechanism of BDNF on neurotoxicity was evaluated using CATH.a cells, a clonal catecholaminergic cell line derived from the central nervous system. Dopamine produced a dose-dependent cell death in CATH.a cells. Treatment of CATH.a cells with BDNF or glia cell line-derived neurotrophic factor (GDNF) reduced dopamine-induced cell death by approximately 60-70%. Nerve growth factor, basic fibroblast growth factor, neurotrophin-4/5 and insulin had no protective effect on dopamine-induced cell death. Dopamine decreased the activity of superoxide dismutase and the levels of glutathione in the CATH.a cells and these decreases were reversed by BDNF. In addition, BDNF treatment alone increased superoxide dismutase activity by 108%. These results suggest that BDNF may safeguard CATH.a cells from dopamine-induced cell death by maintaining or enhancing components of the cell, which protect from oxidative stress.
Gong
L
L
National Institute of Mental Health, Neuropsychiatry Branch, Bethesda, MD 20892-2668, USA.
Wyatt
R J
RJ
Baker
I
I
Masserano
J M
JM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002490:Central Nervous System; D004298:Dopamine / Q000633:toxicity*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005978:Glutathione / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007328:Insulin; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D013482:Superoxide Dismutase; D005978:Glutathione; C073922:neurotrophin 4; D004298:Dopamine