Fine ultrastructure and biochemistry of PC12 cells: a comparative approach to understand neurotoxicity.
The PC12 cell line is commonly used as a tool to understand the biochemical mechanisms underlying the physiology and degeneration of central dopamine neurons. Despite the broad use of this cell line, there are a number of points differing between PC12 cells and dopamine neurons in vivo which are missed out when translating in vitro data into in vivo systems. This led us to compare the PC12 cells with central dopamine neurons, aiming at those features which are predictors of in vivo physiology and degeneration of central dopamine neurons. We carried out this comparison, either in baseline conditions, following releasing or neurotoxic stimuli (i.e. acute or chronic methamphetamine), to end up with therapeutic agents which are suspected to produce neurotoxicity (l-DOPA). Although the neurotransmitter pattern of PC12 cells is close to dopamine neurons, ultrastructural morphometry demonstrates that, in baseline conditions, PC12 cells possess very low vesicles density, which parallels low catecholamine levels. Again, compartmentalization of secretory elements in PC12 cells is already pronounced in baseline conditions, while it is only slightly affected following catecholamine-releasing stimuli. This low flexibility is caused by the low ability of PC12 cells to compensate for sustained catecholamine release, due both to non-sufficient dopamine synthesis and poor dopamine storage mechanisms. This contrasts markedly with dopamine-containing neurons in vivo lending substance to opposite findings between these compartments concerning the sensitivity to a number of neurotoxins.
Fornai
Francesco
F
Department of Human Morphology and Applied Biology, University of Pisa, Pisa I-56126, Italy. f.fornai@med.unipi.it
Lenzi
Paola
P
Lazzeri
Gloria
G
Ferrucci
Michela
M
Fulceri
Federica
F
Giorgi
Filippo S
FS
Falleni
Alessandra
A
Ruggieri
Stefano
S
Paparelli
Antonio
A
D000313:Adrenal Medulla / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity; D007150:Immunohistochemistry; D007980:Levodopa / Q000633:toxicity; D008297:Male; D008636:Mesencephalon / Q000378:metabolism* / Q000648:ultrastructure; D008694:Methamphetamine / Q000633:toxicity; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity; D016716:PC12 Cells; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002395:Catecholamines; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D009498:Neurotoxins; D008694:Methamphetamine; D007980:Levodopa; D004298:Dopamine