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

Bambang Wispriyono, Eva M. Schmelz, Homer Pelayo, Kentaro Hanada, Duska Separovic

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

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 by the de novo sphingolipid synthesis inhibitor ISP-1 (Myriocin). Coincubation with sphinganine, sphingosine, or C16-ceramide specifically reversed the antiapoptotic actions of ISP-1 or the singlet oxygen scavenger L-histidine. PDT-induced cytochrome c release from mitochondria into the cytosol was inhibited by L-histidine, but not by ISP-1. Cotreatment with sphinganine did not reverse the inhibitory effect of L-histidine. In addition, PDT-induced sphinganine accumulation and apoptosis were ISP-1-sensitive in A431 human epidermoid and HT29 human carcinoma cells. Furthermore, in LY-B cells, CHO-derived mutants deficient in the de novo sphingolipid synthesis enzyme serine palmitoyltrans-ferase (SPT) activity, DEVDase activation and apoptosis were delayed and suppressed post-PDT. Hence, the data are consistent with the partial involvement of the de novo sphingolipid pathway in apoptosis via DEV-Dase activation downstream of mitochondrial cytochrome c release post-Pc 4-PDT.

Original languageEnglish
Pages (from-to)153-165
Number of pages13
JournalExperimental Cell Research
Volume279
Issue number1
DOIs
Publication statusPublished - 1 Jan 2002

Keywords

  • Apoptosis
  • Oxidative stress
  • Pc 4
  • Photodynamic therapy
  • Singlet oxygen
  • Sphingolipids

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