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Phosphorylation and activation of p70 S6 kinase by manganese in PC12 cells
1Laboratory for Genes of Motor Systems, Bio-Mimetic Control Research Center, The Institute of Physical and Chemical Research (RIKEN), Moriyama, Nagoya, Japan.
Abstract:
Previous study has shown that the treatment of PC12 cells with manganese, a MPTP-like neurotoxin, causes transcription-dependent apoptosis. This is a useful model system for the study of neuronal cell death. Manganese-induced apoptosis is accompanied by the induction of DNA fragmentation, expressions of c-Fos and c-Jun, and activation of the c-Jun N-terminal kinase U(JNK) pathway. Here, we report that manganese induces phosphorylation of p70 S6 kinase at Ser411 and Thr421/Ser424, and activates the enzyme. Thus, phosphorylation and activation of p70 S6 kinase are accompanied by transcription-dependent apoptosis, suggesting a role for p70 S6 kinase in this type of apoptosis.
Insights
Manganese exposure triggers transcription-dependent apoptosis in PC12 cells. This study reveals that p70 S6 kinase activation is involved in this neurotoxic process, suggesting a new target for understanding neuronal cell death.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- MPTP-like neurotoxins, such as manganese, induce apoptosis in neuronal cells.
- Manganese-induced apoptosis in PC12 cells involves DNA fragmentation, c-Fos/c-Jun expression, and JNK pathway activation.
- The role of p70 S6 kinase in this specific apoptotic pathway remains unclear.
Purpose of the Study:
- To investigate the role of p70 S6 kinase in manganese-induced transcription-dependent apoptosis in PC12 cells.
- To determine if manganese exposure leads to the activation of p70 S6 kinase.
Main Methods:
- Treatment of PC12 cells with manganese.
- Analysis of p70 S6 kinase phosphorylation at specific sites (Ser411 and Thr421/Ser424).
- Assessment of p70 S6 kinase enzyme activity.
Main Results:
- Manganese treatment induced phosphorylation of p70 S6 kinase at Ser411 and Thr421/Ser424.
- The phosphorylation correlated with the activation of p70 S6 kinase.
- p70 S6 kinase activation occurred concurrently with transcription-dependent apoptosis.
Conclusions:
- Phosphorylation and activation of p70 S6 kinase are associated with manganese-induced transcription-dependent apoptosis.
- p70 S6 kinase may play a significant role in this model of neuronal cell death.
- Further research into p70 S6 kinase function could elucidate mechanisms of neurotoxicity.