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Role of sphingomyelin synthase in ceramide production and apoptosis after photodamage
Author(s) -
Separovic Duska,
Maitah Ma'in Yehya Awad,
Hanada Kentaro,
Bielawski Jacek
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a606-d
Subject(s) - ceramide , sphingomyelin , sphingolipid , jurkat cells , apoptosis , lipid signaling , sphingosine , chemistry , transfection , sphingomyelin phosphodiesterase , ceramide synthase , microbiology and biotechnology , biology , biochemistry , enzyme , immunology , cholesterol , receptor , immune system , t cell , gene
During apoptosis after photodamage with the photosensitizer Pc 4 (PDT) increased ceramide levels are observed. We have also shown that PDT inhibits sphingomyelin synthase (SMS), an enzyme that converts de novo‐generated ceramide into sphingomyelin, with concomitant increase in de novo ceramide. In this study the role of SMS in ceramide metabolism and apoptosis after PDT was determined directly. Jurkat T lymphoma/leukemia cells transfected with SMS or empty vector were generated, sphingolipid mass was determined using high‐performance liquid chromatography‐tandem mass spectrometry, and caspase‐3‐like activity (DEVDase) was measured using spectrofluorimetric assay. In SMS‐overexpressors increases in ceramides were lower than in empty vector‐transfectants after PDT. Similarly, the response of dihydroceramides, metabolites in the de novo ceramide pathway, was attenuated in SMS‐overexpressors compared to empty vector‐transfectants after PDT, suggesting the involvement of the de novo pathway. Sphingomyelin mass was unaffected in empty vector‐transfectants, whereas the sphingolipid response was inhibited in SMS‐overexpressors following photodamage. Concomitant with the suppressed ceramide response, DEVDase activation was reduced in SMS‐overexpressors. The data show that SMS is a regulator of ceramide metabolism and apoptosis after photodamage. These findings suggest that SMS is a potential novel molecular target that can affect the therapeutic efficacy of PDT.