期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 113, 期 3, 页码 169-181出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0047-6374(99)00105-0
关键词
ceramide; senescence; beta-galactosidase; sphingolipid; fibroblast
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-C-6-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 C-6-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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
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