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KMID : 0624620190520030220
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BMB Reports
2019 Volume.52 No. 3 p.220 ~ p.225
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Links between accelerated replicative cellular senescence and down-regulation of SPHK1 transcription
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Kim Min-Kyung
Lee Woo-Seong
Yoon Gang-Ho
Chang Eun-Ju
Choi Sun-Cheol
Kim Seong-Who
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Abstract
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We have identified a mechanism to diminish the proliferative capacity of cells during cell expansion using human adiposederived stromal cells (hAD-SCs) as a model of replicative senescence. hAD-SCs of high-passage numbers exhibited a reduced proliferative capacity with accelerated cellular senescence. Levels of key bioactive sphingolipids were significantly increased in these senescent hAD-SCs. Notably, the transcription of sphingosine kinase 1 (SPHK1) was down-regulated in hAD-SCs at high-passage numbers. SPHK1 knockdown as well as inhibition of its enzymatic activity impeded the proliferation of hAD-SCs, with concomitant induction of cellular senescence and accumulation of sphingolipids, as seen in high-passage cells. SPHK1 knockdown-accelerated cellular senescence was attenuated by co-treatment with sphingosine-1-phosphate and an inhibitor of ceramide synthesis, fumonisin B1, but not by treatment with either one alone. Together, these results suggest that transcriptional down-regulation of SPHK1 is a critical inducer of altered sphingolipid profiles and enhances replicative senescence during multiple rounds of cell division.
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KEYWORD
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Human adipose-derived stromal cells, Replicative senescence, Sphingolipid, Sphingosine kinase 1, SPHK1 transcription
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