Ceramide does not act as a general second messenger for ultraviolet-induced apoptosis.
Ceramide has been proposed as a second messenger for stress-induced apoptosis. By characterization of murine melanoma cells and their E1A transfectants, we found several lines of evidences against the role of ceramide as a second messenger for ultraviolet (UV)-induced apoptosis. First, although E1A transfected melanoma cells were more sensitive to UV-induced apoptosis than parental cells, the relative endogenous ceramide elevation induced by UV was greater in parental cells than in E1A transfectants. Second, UV-resistant melanoma cells were more sensitive to exogenous ceramide than UV-sensitive E1A transfectants. The differential responses to UV and ceramide by E1A require the same functional CR2 domain of E1A. Third, unlike the action of UV, transient exposure (up to 2 h) of lethal dose of ceramide was not sufficient to cause apoptosis in these cells, and persistent presence of ceramide was required for processing the apoptotic process. Finally, ceramide and UV do not share a common pathway in apoptosis induction. UV-induced apoptosis was blocked by interleukin-1beta-converting enzyme (ICE) inhibitor z-VAD whereas ceramide-induced apoptosis was not. Therefore, we conclude that ceramide is not a general second messenger for UV-induced apoptosis.
Deng
Jiong
J
Department of Molecular and Cellular Oncology, Box 108, The University of Texas, MD Anderson Cancer Center, Houston, Texas, TX 77030, USA.
Zhang
Haifan
H
Kloosterboer
Freke
F
Liao
Yong
Y
Klostergaard
Jim
J
Levitt
Mark L
ML
Hung
Mien-Chie
MC
D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology; D020170:Caspase 1 / Q000502:physiology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D002518:Ceramides / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D017434:Protein Structure, Tertiary; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015290:Second Messenger Systems; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
D017500:Adenovirus E1A Proteins; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D002518:Ceramides; D004791:Enzyme Inhibitors; C064769:N-acetylsphingosine; D011993:Recombinant Fusion Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D013110:Sphingosine