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TGFb‐HIPK2 Signaling Pathway in the Survival of Dopamine Neurons During Toxin‐induced Degeneration
Author(s) -
Zhang Jiasheng,
Huang Eric J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.58.11
Subject(s) - mptp , phosphorylation , programmed cell death , microbiology and biotechnology , biology , chemistry , dopamine , neuroscience , apoptosis , biochemistry , dopaminergic
The current study investigates TGFb‐HIPK2 signaling pathway in MPTP‐induced degeneration of DA neurons. Our results indicate that loss of HIPK2 leads to a near complete protection of DA neurons from MPTP‐induced cell death. Whereas MPTP treatment induces a robust increase in c‐jun phosphorylation after MPTP in wild type DA neurons, no phospho‐c‐jun is detected in the DA neurons of Hipk2 mutants. To determine if HIPK2 is sufficient for MPTP‐induced cell death, we used a genetic approach to selectively express additional copies of HIPK2 in DA neurons. Our results indicate that DA neurons in conditional mouse mutants expressing extra copies of HIPK2 show a dose‐dependent increase in MPTP‐induced cell loss. Taken together, these results support the notion that, HIPK2 is a key upstream regulator in JNK‐dependent activation of c‐jun phosphorylation and MPTP‐induced cell death in DA neurons. Our results further suggest that TGFb‐HIPK2 signaling pathway may serve as a therapeutic target to support the survival of DA neurons in MPTP‐induced degeneration.