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- Title
GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathway.
- Authors
Li-Ying Yu, Daniel J.; Eija Jokitalo, Daniel J.; Yun-Fu Sun, Daniel J.; Mehlen, Patrick; Lindholm, Dan; Saarma, Mart; Arumäe, Urmas
- Abstract
The mitochondrial death pathway is triggered in cultured sympathetic neurons by deprivation of nerve growth factor (NGF), but the death mechanisms activated by deprivation of other neurotrophic factors are poorly studied. We compared sympathetic neurons deprived of NGF to those deprived of glial cell line-derived neurotrophic factor (GDNE). In contrast to NGF-deprived neurons, GDNE-deprived neurons did not die via the mitochondrial pathway. Indeed, cytochrome c was not released to the cytosol; Bax and caspase-9 and -3 were not involved; overexpressed Bcl-x[subL] did not block the death; and the mitochondrial ultra-structure was not changed. Similarly to NGF-deprived neurons, the death induced by GDNF removal is associated with increased autophagy and requires multiple lineage kinases, c-Jun and caspase-2 and -7. Serine 73 of c-Jun was phosphorylated in both NGF- and GDNF-deprived neurons, whereas serine 63 was phosphorylated only in NGF-deprived neurons. In many NGE-deprived neurons, the ultrastructure of the mitochondria was changed. Thus, a novel nonmito-chondrial caspase-dependent death pathway is activated in GDNF-deprived sympathetic neurons.
- Subjects
MITOCHONDRIA; NERVE growth factor; NEURONS; PHOSPHORYLASES; CYTOCHROME c; ORGANELLES
- Publication
Journal of Cell Biology, 2003, Vol 163, Issue 5, p987
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200305083