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.
PKCζ protects against UV-C-induced apoptosis by inhibiting acid sphingomyelinase-dependent ceramide production
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
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