p38α and p38β regulate osmostress-induced apoptosis
Nabil Ben Messaoud1, José M López1
1Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultad de Medicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.
The Journal of Biological Chemistry
|December 9, 2024
Summary
Hyperosmotic shock triggers apoptosis in Xenopus oocytes via mitochondrial pathways. Specific p38 isoforms (p38α, p38β) and their sustained activation accelerate this osmostress-induced cell death process.
Area of Science:
- Cell Biology
- Molecular Biology
- Apoptosis Research
Background:
- Hyperosmotic shock initiates cell death pathways in Xenopus oocytes, involving mitochondria.
- Mitogen-activated protein kinases (MAPKs), including JNK1-1 and JNK1-2, are activated early by osmostress.
- While sustained JNK activation accelerates apoptosis, the specific p38 isoforms involved in osmostress-induced cell death remain poorly characterized.
Purpose of the Study:
- To investigate the expression and activation patterns of Xenopus p38 isoforms under hyperosmotic stress.
- To elucidate the role of specific p38 isoforms in accelerating osmostress-induced apoptosis.
- To explore the interplay between caspases and p38 kinases in the apoptotic feedback loop.
Main Methods:
- Hyperosmotic shock applied to Xenopus oocytes.
- Analysis of p38 isoform expression and activation.
- Microinjection of cytochrome c to assess caspase-3 activation and p38 phosphorylation.
Main Results:
- p38α, p38β, and p38γ isoforms are rapidly activated by hyperosmotic shock.
- Sustained activation of p38α and p38β significantly accelerates osmostress-induced apoptosis.
- Cytochrome c injection leads to caspase-3 activation and p38α/p38β phosphorylation, indicating a positive feedback loop.
Conclusions:
- Osmostress-induced apoptosis in Xenopus oocytes involves early activation of multiple p38 isoforms.
- Sustained p38α and p38β activity plays a key role in accelerating the apoptotic process.
- A positive feedback mechanism exists between caspases and p38 kinases, amplifying cell death signaling.
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