Induction of mitosis-related genes during dopamine-triggered apoptosis in sympathetic neurons.
It was suggested that neuronal degeneration in Parkinson's Disease (PD) is linked to dopamine (DA) toxicity. Dopamine has been shown to induce programmed cell death in both neuronal and non-neuronal cell types. We examined the molecular changes associated with dopamine-triggered apoptosis in sympathetic neurons using the differential display approach, and isolated 14 different DA responsive genes whose expression is altered during the early stages of the apoptotic process. Nine of these genes are upregulated and five are downregulated in response to DA exposure. Two of the upregulated genes were identified as cyclin B2 and a chicken homologue of chaperonin, a member of the heat shock protein family. Total increase in mRNA expression of both genes after 12 hours of exposure to DA was 40%. These two genes participate in cell cycle control and are specifically involved in determining entry of dividing cells into mitosis. Upregulation of mitosis-related genes in postmitotic sympathetic neurons undergoing apoptosis, may be indicative of an abortive attempt of these neurons to re-enter the cell cycle prior to their death. Possible implications to neuronal degeneration in PD are discussed.
Shirvan
A
A
Felsenstein Medical Research Center, Rabin Medical Center (Beilinson Campus), Petah Tikva, Israel.
Ziv
I
I
Barzilai
A
A
Djaldeti
R
R
Zilkh-Falb
R
R
Michlin
T
T
Melamed
E
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D018833:Chaperonins / Q000096:biosynthesis; D002645:Chickens; D003001:Cloning, Molecular; D016213:Cyclins / Q000096:biosynthesis; D017931:DNA Primers; D004298:Dopamine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008938:Mitosis; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*
D016213:Cyclins; D017931:DNA Primers; D009498:Neurotoxins; D012333:RNA, Messenger; D018833:Chaperonins; D004298:Dopamine