Journal
JOURNAL OF NEUROCHEMISTRY
Volume 99, Issue 1, Pages 218-225Publisher
WILEY
DOI: 10.1111/j.1471-4159.2006.04116.x
Keywords
apoptosis; ataxia telangiectasia-mutated; neuron; protein kinase C; protein kinase C mu
Categories
Funding
- NIA NIH HHS [R37AG-12947] Funding Source: Medline
- NINDS NIH HHS [R01NS38651] Funding Source: Medline
Ask authors/readers for more resources
In neurons, DNA damage induces protein synthesis-dependent apoptosis mediated by the mitochondrial intrinsic cell-death pathway. Signal transduction cascades activated by genotoxic stress upstream of the mitochondria are largely unknown. We identified protein kinase D (PKD) as one of the earliest markers of neuronal DNA damage. Phosphorylation of the PKD-activation domain could be detected within 15 min of genotoxic stress and was concurrent with ataxia telangiectasia-mutated (ATM) activation. PKD stimulation was selective to DNA damage and did not occur with other stress stimuli examined. In vivo, both young and adult rats showed increased levels of phosphorylated PKD in neuronal tissues after injection of DNA-toxin etoposide. These results indicate that PKD activation is an early neuronal response to DNA damage, suggesting that signaling downstream of PKD may be critical for neuronal survival after genotoxic stress.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available