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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Two distinct signaling pathways regulate peroxynitrite-induced apoptosis in PC12 cells
J J Shacka1, M A Garner, J D Gonzalez
1Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, USA.
Cell Death and Differentiation
|January 18, 2006
Summary
Peroxynitrite triggers cell death by activating p38 and JNK MAP kinases, which initiate the intrinsic apoptotic pathway. This process involves the Akt pathway and is crucial for understanding cell death mechanisms.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Peroxynitrite is a reactive nitrogen species implicated in cellular damage.
- The precise mechanisms of peroxynitrite-induced apoptosis remain incompletely elucidated.
- Understanding these pathways is critical for neuroprotection and disease research.
Purpose of the Study:
- To investigate the signaling pathways involved in peroxynitrite-induced apoptosis in PC12 cells.
- To elucidate the roles of MAP kinases (p38, JNK) and the Akt pathway in this process.
- To identify key molecular events leading to cell death.
Main Methods:
- Utilized PC12 cell lines for apoptosis studies.
- Employed techniques such as Western blotting to assess protein phosphorylation and translocation.
- Investigated the effects of specific kinase inhibitors and genetic manipulations (overexpression).
Main Results:
- Peroxynitrite-induced apoptosis necessitates co-activation of p38 and JNK MAP kinases.
- Activation of the intrinsic apoptotic pathway (Bax translocation, cytochrome c release, caspase activation) was observed.
- Peroxynitrite induced Akt pathway inactivation, which was reversed by constitutively active Akt.
- Inhibition of MLK/MAPK pathways did not affect Akt inactivation, indicating pathway independence.
Conclusions:
- Peroxynitrite triggers apoptosis via the intrinsic pathway, mediated by p38 and JNK MAP kinase activation.
- The Akt pathway is inactivated independently of the MLK/MAPK pathway during peroxynitrite-induced cell death.
- These findings reveal complex crosstalk between MLK/MAPK and Akt signaling in regulating apoptosis.
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