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

O'Malley, KL; Liu, J; Lotharius, Julie LU and Holtz, W (2003) In Neurobiology of Disease 14(1). p.43-51
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... (More)
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. (C) 2003 Elsevier Science (USA). All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurobiology of Disease
volume
14
issue
1
pages
43 - 51
publisher
Elsevier
external identifiers
  • pmid:13678665
  • wos:000185438700005
  • scopus:0042334593
ISSN
0969-9961
DOI
10.1016/S0969-9961(03)00013-5
language
English
LU publication?
yes
id
45585698-8a4d-4db4-919a-ebfc3d5090cc (old id 300026)
date added to LUP
2007-09-19 14:59:44
date last changed
2018-10-03 10:21:17
@article{45585698-8a4d-4db4-919a-ebfc3d5090cc,
  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. (C) 2003 Elsevier Science (USA). All rights reserved.},
  author       = {O'Malley, KL and Liu, J and Lotharius, Julie and Holtz, W},
  issn         = {0969-9961},
  language     = {eng},
  number       = {1},
  pages        = {43--51},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Targeted expression of BCL-2 attenuates MPP+ but not 6-OHDA induced cell death in dopaminergic neurons},
  url          = {http://dx.doi.org/10.1016/S0969-9961(03)00013-5},
  volume       = {14},
  year         = {2003},
}