Prostaglandins antagonistically control Bax activation during apoptosis - Archive ouverte HAL Access content directly
Journal Articles Cell Death and Differentiation Year : 2010

Prostaglandins antagonistically control Bax activation during apoptosis

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Pierre-François Cartron
Christophe Olivier
  • Function : Author
  • PersonId : 1071511
Cedric Logé
  • Function : Author
Gwenola Bougras
  • Function : Author
Jean-Michel Robert
  • Function : Author
Lisa Oliver
  • Function : Author
Francois M Vallette
  • Function : Correspondent author
  • PersonId : 899658

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Abstract

The Bax protein (Bcl-2-associated X protein) is pivotal for the apoptotic process. Bax, which resides in an inactive form in the cytosol of healthy cells, is activated during the early stages of apoptosis and becomes associated with mitochondria through poorly understood mechanisms. Here we show that a family of bioactive lipids, namely prostaglandins, regulates Bax-dependent apoptosis. The prostaglandin E2 (PGE2) or its derivative PGA2 binds to Bax, induces its change of conformation, and thereby triggers apoptosis. A cysteine present in the loop between the two transmembrane alpha helices of Bax, Cys126 is critical for its activation. PGD2 inhibited PGE2 binding to Bax and PGE2-induced apoptosis, as well as cell death induced by staurosporine and UV-B in various cell lines. This result is consistent with the fact that apoptosis is accompanied during these treatments by an increase in PGE2. This process is distinct, yet cooperative, from that involving the BH3-only protein Bid. Our results establish that the PGE2/PGD2 balance is involved in a new early mechanism of control in the activation of Bax during apoptosis.
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hal-00587969 , version 1 (22-04-2011)

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Lisenn Lalier, Pierre-François Cartron, Christophe Olivier, Cedric Logé, Gwenola Bougras, et al.. Prostaglandins antagonistically control Bax activation during apoptosis. Cell Death and Differentiation, 2010, ⟨10.1038/cdd.2010.128⟩. ⟨hal-00587969⟩
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