Hyperosmotic Shock Engages Two Positive Feedback Loops through Caspase-3-dependent Proteolysis of JNK1-2 and Bid

Hyperosmotic shock induces early calpain activation, Smac/DIABLO release from the mitochondria, and p38/JNK activation in Xenopus oocytes. These pathways regulate late cytochrome c release and caspase-3 activation. Here, we show that JNK1-1 and JNK1-2 are activated early by osmostress, and sustained...

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Bibliographic Details
Published in:The Journal of biological chemistry 2015-12, Vol.290 (51), p.30375-30389
Main Authors: Yue, Jicheng, Ben Messaoud, Nabil, López, José M.
Format: Article
Language:English
Subjects:
Animals
apoptosis
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Bid
c-Jun N-terminal kinase (JNK)
Caspase 3 - genetics
Caspase 3 - metabolism
Enzyme Activation
Humans
Isoenzymes - genetics
Isoenzymes - metabolism
Mitogen-Activated Protein Kinase 8 - genetics
Mitogen-Activated Protein Kinase 8 - metabolism
Molecular Bases of Disease
oocyte
Oocytes - cytology
Oocytes - metabolism
osmostress
Osmotic Pressure - physiology
protein kinase
Proteolysis
Signal Transduction
signaling
ubiquitylation (ubiquitination)
Xenopus laevis
Xenopus Proteins - genetics
Xenopus Proteins - metabolism
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Summary:Hyperosmotic shock induces early calpain activation, Smac/DIABLO release from the mitochondria, and p38/JNK activation in Xenopus oocytes. These pathways regulate late cytochrome c release and caspase-3 activation. Here, we show that JNK1-1 and JNK1-2 are activated early by osmostress, and sustained activation of both isoforms accelerates the apoptotic program. When caspase-3 is activated, JNK1-2 is proteolyzed at Asp-385 increasing the release of cytochrome c and caspase-3 activity, thereby creating a positive feedback loop. Expression of Bcl-xL markedly reduces hyperosmotic shock-induced apoptosis. In contrast, expression of Bid induces rapid caspase-3 activation, even in the absence of osmostress, which is blocked by Bcl-xL co-expression. In these conditions a significant amount of Bid in the cytosol is mono- and bi-ubiquitinated. Caspase-3 activation by hyperosmotic shock induces proteolysis of Bid and mono-ubiquitinated Bid at Asp-52 increasing the release of cytochrome c and caspase-3 activation, and thus creating a second positive feedback loop. Revealing the JNK isoforms and the loops activated by osmostress could help to design better treatments for human diseases caused by perturbations in fluid osmolarity.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M115.660506