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.
Abstract:
Hyperosmotic shock induces cytochrome c release and caspase-3 activation in Xenopus oocytes. Different signaling pathways engaged by osmostress converge on the mitochondria to trigger cell death. The mitogen-activated protein kinases (MAPKs) JNK1-1 and JNK1-2 are early activated by hyperosmotic shock and sustained activation of both isoforms accelerates the apoptotic program. Indeed, sustained activation of p38 accelerates osmostress-induced cell death, but the p38 isoforms involved are not well characterized. Here we study the expression and activation of Xenopus p38 isoforms in response to hyperosmotic stress. We find that p38α, p38β, and p38γ are early activated by hyperosmotic shock and sustained activation of p38α and p38β accelerates osmostress-induced apoptosis. Moreover, microinjection of cytochrome c in the oocytes induces caspase-3 activation and p38α and p38β phosphorylation suggesting that caspases and kinases are interlinked in a positive feedback loop to promote cell death. In summary, we present a more complete view of the mechanisms involved in osmostress-induced apoptosis.
Insights
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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