UV-C light induces raft-associated acid sphingomyelinase and JNK activation and translocation independently on a nuclear signal.
The initiation of UV light-induced signaling in mammalian cells is largely considered to be subsequent to DNA damage. Several studies have also described ceramide (CER), a lipid second messenger, as a major contributor in mediating UV light-induced c-Jun N-terminal kinase (JNK) activation and cell death. It is demonstrated here that UV-C light irradiation of U937 cells results in the activation and translocation of a Zn2+-independent acid sphingomyelinase, leading to CER accumulation in raft microdomains. These CER-enriched rafts aggregate and play a functional role in JNK activation. The observation that UV-C light also induced CER generation and the externalization of acid sphingomyelinase and JNK in human platelets conclusively rules out the involvement of a nuclear signal generated by DNA damage in the initiation of a UV light response, which is generated at the plasma membrane.
Charruyer
Alexandra
A
INSERM U563, Centre de Physiopathologie de Toulouse-Purpan, Centre Hospitalier Universitaire Purpan, 31024 Toulouse, France.
Grazide
Solène
S
Bezombes
Christine
C
Müller
Sabina
S
Laurent
Guy
G
Jaffrézou
Jean-Pierre
JP
D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002469:Cell Separation; D002518:Ceramides / Q000378:metabolism; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006868:Hydrolysis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D021962:Membrane Microdomains / Q000737:chemistry*; D018613:Microscopy, Confocal; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D021381:Protein Transport; D017382:Reactive Oxygen Species; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013997:Time Factors; D020298:U937 Cells; D014466:Ultraviolet Rays; D015032:Zinc / Q000737:chemistry
D002518:Ceramides; D017382:Reactive Oxygen Species; D013109:Sphingomyelins; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D013108:Sphingomyelin Phosphodiesterase; D015032:Zinc