Ceramide induces expression of the senescence histochemical marker, beta-galactosidase, in human fibroblasts.
We recently showed that ceramide is elevated in senescence and that when administered to low-passage cells induces biochemical changes characteristic of senescence. The in situ histochemical marker beta-galactosidase (beta-Gal) has provided an important tool in the study of cellular senescence. We investigated the ability of ceramide to induce the expression of beta-Gal and correlated this with cell proliferation. We find that D-e-C6-ceramide, induces the expression of acidic beta-Gal in fetal lung-derived Wi-38 human diploid fibroblasts. Our results show that this induction is: (1) time and concentration dependent; and (2) reversible upon ceramide removal. We also find that concomitant with the onset of beta-Gal staining, DNA synthesis is blocked. These conditions are reversible. The induction of beta-Gal expression is specific to C6-ceramide. We discuss a potential role of beta-Gal in the regulation of senescence. Although signal transduction of senescence is still not fully understood, this new evidence strengthens the hypothesis that ceramide plays a key role in signaling down stream biochemical changes in cellular senescence.
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Biology Department, Appalachian State University, Boone, NC 28608-2027, USA.
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D015415:Biomarkers; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology*; D002518:Ceramides / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000096:biosynthesis*
D015415:Biomarkers; D002518:Ceramides; C101954:N-caproylsphingosine; D004247:DNA; D001616:beta-Galactosidase