In a recent study, we described that UV-C irradiation resulted in redox-dependent activation and relocalization of A-SMase (acid sphingomyelinase) to the external surface of raft membrane microdomains, hydrolysis of SM (sphingomyelin) associated with the plasma membrane outer leaflet, ceramide generation and apoptosis. In the present study, we have investigated the influence of PKCζ (protein kinase Cζ), an atypical form of PKC on this pathway. This study shows that PKCζ overexpression resulted in the abrogation of UV-C-induced A-SMase translocation and activation into the raft microdomains, lack of ceramide generation and apoptosis inhibition. Moreover, PKCζ overexpression resulted in a decrease in UV-C-induced ROS (reactive oxygen species) production, which correlated with increased gene expression level of various antioxidant enzymes, including TRx (thioredoxin), TR (thioredoxin reductase) 1, TR2 and peroxiredoxin 1/TPx2 (thioredoxin peroxidase 2). Importantly, enforced TPx2 gene expression inhibited UV-C-induced A-SMase translocation. Finally, PKCζ inhibition led to a significant reduction in TPx2 protein expression. Altogether, these results suggest that PKCζ interferes with the UV-activated sphingolipid signalling pathway by regulating the TRx system. These findings may have important consequences for UV-induced carcinogenesis and resistance to phototherapy.
Skip Nav Destination
Article navigation
July 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
June 13 2007
PKCζ protects against UV-C-induced apoptosis by inhibiting acid sphingomyelinase-dependent ceramide production
Alexandra Charruyer;
Alexandra Charruyer
*Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France
†Université Toulouse III Paul Sabatier, Toulouse, F-31400, France
Search for other works by this author on:
Christine Jean;
Christine Jean
*Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France
†Université Toulouse III Paul Sabatier, Toulouse, F-31400, France
Search for other works by this author on:
Audrey Colomba;
Audrey Colomba
*Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France
†Université Toulouse III Paul Sabatier, Toulouse, F-31400, France
Search for other works by this author on:
Jean-Pierre Jaffrézou;
Jean-Pierre Jaffrézou
*Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France
†Université Toulouse III Paul Sabatier, Toulouse, F-31400, France
Search for other works by this author on:
Anne Quillet-Mary;
Anne Quillet-Mary
*Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France
†Université Toulouse III Paul Sabatier, Toulouse, F-31400, France
Search for other works by this author on:
Guy Laurent;
Guy Laurent
*Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France
‡CHU Toulouse, Hôpital Purpan, Service d'Hématologie, Toulouse, F-31300, France
Search for other works by this author on:
Christine Bezombes
Christine Bezombes
1
*Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France
†Université Toulouse III Paul Sabatier, Toulouse, F-31400, France
1To whom correspondence should be addressed (email christine.bezombes-cagnac@toulouse.inserm.fr).
Search for other works by this author on:
Biochem J (2007) 405 (1): 77–83.
Article history
Received:
October 10 2006
Revision Received:
February 21 2007
Accepted:
March 08 2007
Accepted Manuscript online:
March 08 2007
Citation
Alexandra Charruyer, Christine Jean, Audrey Colomba, Jean-Pierre Jaffrézou, Anne Quillet-Mary, Guy Laurent, Christine Bezombes; PKCζ protects against UV-C-induced apoptosis by inhibiting acid sphingomyelinase-dependent ceramide production. Biochem J 1 July 2007; 405 (1): 77–83. doi: https://doi.org/10.1042/BJ20061528
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.