Targeted expression of BCL-2 attenuates MPP+ but not 6-OHDA induced cell death in dopaminergic neurons

Karen L. O'Malley, Jian Liu, Julie Lotharius, William Holtz

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Neurodegenerative diseases such as Parkinson's disease exhibit complex features of cell death reflecting both the primary lesion as well as surrounding interconnected events. Because Bcl-2 family members are intimately involved in cell death processes, the present study used dopaminergic cultures from control, Bcl-2-overexpressing, or Bax-deficient genetically modified animals to determine the in situ effects of parkinsonism-inducing toxins. MPP+-mediated cell death was attenuated by Bcl-2 but did not require Bax. Accordingly, mutations or deletions within Bax heterodimerization domains, BH1, BH2, or BH3 had no effect on Bcl-2's ability to prevent cell death, whereas the cell-death suppressing BH4 domain did. Although both staurosporine and 6-OHDA induced apoptosis, overexpression of Bcl-2 only rescued cells from programmed cell death induced by staurosporine. Thus, differential cell death pathways are associated with these cytotoxic signals in primary models of Parkinson's disease.

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalNeurobiology of Disease
Volume14
Issue number1
DOIs
StatePublished - Oct 2003

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