A role for the de novo sphingolipids in apoptosis of photosensitized cells.

@article{Wispriyono2002ARF,
  title={A role for the de novo sphingolipids in apoptosis of photosensitized cells.},
  author={Bambang Wispriyono and Eva M. Schmelz and Homer Pelayo and Kentaro Hanada and Duska Separovic},
  journal={Experimental cell research},
  year={2002},
  volume={279 1},
  pages={
          153-65
        }
}
Sphingolipids have been implicated in apoptosis after various stress inducers. To assess the involvement of the de novo sphingolipid pathway in apoptosis, photodynamic therapy (PDT) with the photosensitizer Pc 4 was used as a novel stress inducer. Here we provide biochemical and genetic evidence of the role of the de novo sphingolipids in apoptosis post-Pc 4-PDT. In Jurkat cells PDT-induced intracellular sphinganine accumulation, DEVDase activation, PARP cleavage, and apoptosis were suppressed… Expand
Reactive oxygen species generation is independent of de novo sphingolipids in apoptotic photosensitized cells.
TLDR
The data support the following hypotheses: MnTBAP protects against apoptosis via steps downstream of deltapsi(m) loss; de novo sphingolipids are not required for ROS generation, but can play a role in delTapsi (m) dissipation in photosensitized apoptotic cells. Expand
De Novo Ceramide Accumulation Due to Inhibition of Its Conversion to Complex Sphingolipids in Apoptotic Photosensitized Cells*
TLDR
These results are the first to show that in the absence of SPT up-regulation PDT induces accumulation of de novo ceramide by inhibiting its conversion to complex sphingolipids. Expand
Sphingomyelin synthase 1 suppresses ceramide production and apoptosis post-photodamage.
TLDR
Overexpression of SMS1 was associated with differential regulation of sphingomyelin levels, as well as with the reduced inhibition of the enzyme post-treatment, and PDT-induced DEVDase activation was substantially reduced in SMS1-overexpressors. Expand
Ceramide response post-photodamage is absent after treatment with HA14-1.
TLDR
The results show that the ceramide response to PDT is not induced by another pro-apoptotic stimulus, and may be unique to PDT as described here. Expand
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TLDR
The data suggest the involvement of the de novo sphingolipid biosynthesis pathway in enhanced apoptotic cell killing after PDT+HPR, and identify the combination as a novel more effective anticancer treatment than either treatment alone. Expand
Suppression of sphingomyelin synthase 1 by small interference RNA is associated with enhanced ceramide production and apoptosis after photodamage.
TLDR
The data show that RNA interference-dependent downregulation of SMS1 is associated with increased accumulation of ceramide and dihydroceramide with concomitant sensitization of cells to apoptosis after photodamage, and suggest that SMS is a potential novel molecular target that can augment therapeutic efficacy of PDT. Expand
Ceramide synthase inhibitor fumonisin B1 inhibits apoptotic cell death in SCC17B human head and neck squamous carcinoma cells after Pc4 photosensitization.
  • Nithin B. Boppana, M. Kodiha, +8 authors D. Separovic
  • Biology, Medicine
  • Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology
  • 2014
TLDR
Novel data suggest that PDT-induced cell death via apoptosis is CERS/ceramide-dependent, and this study used the silicon phthalocyanine Pc4 for PDT, and SCC17B cells, a clinically-relevant model of human head and neck squamous carcinoma. Expand
Dihydroceramide desaturase knockdown impacts sphingolipids and apoptosis after photodamage in human head and neck squamous carcinoma cells.
TLDR
It is shown that following ceramide synthase knockdown, photodynamic therapy (PDT), a cancer treatment modality, is associated with decreased levels of ceramides and dihydroceramides in cells that are resistant to apoptosis, and DES is a potential molecular target for regulating apoptotic resistance to PDT. Expand
A role for manganese superoxide dismutase in apoptosis after photosensitization.
TLDR
The data show that MnSOD affects sensitivity of cells to Pc 4-PDT-initiated apoptosis, and partly ceramide accumulation, suggesting that the processes are superoxide-mediated. Expand
Regulation of de novo sphingolipid biosynthesis by the ORMDL proteins and sphingosine kinase-1.
TLDR
It is found that de novo synthesis of sphingolipid is stimulated by a number of cancer chemotherapeutics, suggesting that this may be an important aspect of their cytotoxic effects. Expand
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