Functionality of NGF-protected PC12 cells following exposure to 6-hydroxydopamine.
6-Hydroxydopamine (6-OHDA) is often used in models of Parkinson's disease since it can selectively target and kill dopaminergic cells of the substantia nigra. In this study, pre-treatment of PC12 cells with nerve growth factor (NGF) inhibited apoptosis and necrosis by 6-OHDA, including caspase activity and lactate dehydrogenase release. Notably, cells exposed to 6-OHDA in the presence of NGF were subsequently capable of proliferation (when replated without NGF), or neurite outgrowth (with continued presence of NGF). Following 7 days growth in the presence of NGF, expression of betaIII tubulin and tyrosine hydroxylase and increased intracellular catecholamines was detectable in PC12 cells, features characteristic of functional dopaminergic neurons. NGF-pre-treated PC12 cells retained expression of betaIII-tubulin and tyrosine hydroxylase, but not catecholamine content following 6-OHDA exposure. These data indicate that NGF-protected cells maintained some aspects of functionality and were subsequently capable of proliferation or differentiation.
Kavanagh
Edel T
ET
Department of Biochemistry, National University of Ireland, Galway, Ireland.
Loughlin
John P
JP
Herbert
Kate Reed
KR
Dockery
Peter
P
Samali
Afshin
A
Doyle
Karen M
KM
Gorman
Adrienne M
AM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D002395:Catecholamines / Q000032:analysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D009336:Necrosis; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016627:Oxidopamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D014404:Tubulin / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D002395:Catecholamines; D014404:Tubulin; D016627:Oxidopamine; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase