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Volume 149, Issue 8

Bacterial ceramides and sphingophospholipids induce apoptosis of human leukaemic cells Free

Abstract

The genus , whose members are Gram-negative non-fermentative rods, possesses ceramides and related sphingophospholipids (SPLs) with isoheptadecasphinganine and 2-hydroxy or non-hydroxy isopentadecanoic acid. This paper reports evidence that ceramides isolated from ATCC 33861 induce endonucleolytic DNA cleavage in human myeloid leukaemia HL-60 cells , which is the primary characteristic biochemical marker for apoptosis or programmed cell death. Ceramides and SPLs also induced DNA fragmentation and caspase-3 activation, followed by changes in morphology, such as alterations in the size of nuclei and cells, and cell cycle shortening. Apoptotic activity correlated with the ceramide structure. Ceramide with a 2-hydroxy fatty acid showed stronger apoptotic activity than ceramide with a non-hydroxy fatty acid. Furthermore, the major five SPLs (ceramide phosphorylethanolamine-1 and -2, ceramide phosphorylinositol-1 and -2, and ceramide phosphorylmannose-1) showed apoptosis-inducing activity in HL-60 cells, indicating that the ceramide moiety of the SPLs plays a crucial role as the intracellular second messenger but that their hydrophilicity is less important in this regard. The hydrophilic part of SPLs may play a role in other cellular response systems. The involvement of Fas antigen was implicated in the apoptotic event since Fas antigen expression was observed after 3 or 4 h stimulation of HL-60 cells with bacterial ceramides. However, a time-course study for caspase-3 activation indicated maximal activity at 1 h after stimulation with bacterial ceramides, suggesting that two (or possibly more) mechanisms of signal transduction, Fas-dependent and Fas-independent, may be involved. Fas antigen expression and caspase-3 activation by five kinds of SPLs were observed after 3 or 4 h. These results indicate that there is a difference in the response of HL-60 cells to bacterial ceramides and SPLs.

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Keyword(s): AMC, 7-amino-4-methylcoumarin , cer-A, -B, ceramide-A, -B (see text and Fig. 1 for structures), cerPE, ceramide phosphorylethanolamine , cerPI, ceramide phosphorylinositol , cerPM, ceramide phosphorylmannose , FBS, fetal bovine serum and SPL, sphingophospholipid
SGM
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2003-08-01
2025-05-23
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Bacterial ceramides and sphingophospholipids induce apoptosis of human leukaemic cells
Microbiology 149, 2071 (2003); https://doi.org/10.1099/mic.0.25922-0
/content/journal/micro/10.1099/mic.0.25922-0
/content/journal/micro/10.1099/mic.0.25922-0
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