PKCε phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration

Varun Kumar†,
Yi-Chinn Weng†,
Yu-Chieh Wu†,
Yu-Ting Huang and
Wen-Hai ChouEmail author View ORCID ID profile

†Contributed equally

BMC Neuroscience201819:76

https://doi.org/10.1186/s12868-018-0479-z

Received: 10 August 2018
Accepted: 27 November 2018
Published: 29 November 2018

Abstract

Background

Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identified as a master switch that controls the nucleocytoplasmic trafficking of ATF2 and the survival of melanoma cells. It is of interest to assess the role of PKCε–ATF2 signaling in neurodegeneration.

Results

Phosphorylation of ATF2 at Thr-52 was reduced in the hippocampus of PKCε null mice, suggesting that ATF2 is a phosphorylation substrate of PKCε. PKCε protein concentrations were significantly reduced 4, 24, 48 and 72 h after transient global cerebral ischemia, resulting in translocation of nuclear ATF2 to the mitochondria. Degenerating neurons staining positively with Fluoro-Jade C exhibited cytoplasmic ATF2.

Conclusions

Our results support the hypothesis that PKCε regulates phosphorylation and nuclear sequestration of ATF2 in hippocampal neurons during ischemia-induced neurodegeneration.