Links between accelerated replicative cellular senescence and down-regulation of SPHK1 transcription

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 senescenc...

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Veröffentlicht in:BMB Reports 2019, 52(3), , pp.220-225
Hauptverfasser: Kim, Min Kyung, Lee, Wooseong, Yoon, Gang-Ho, Chang, Eun-Ju, Choi, Sun-Cheol, Kim, Seong Who
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Sprache:eng
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Zusammenfassung: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. [BMB Reports 2019; 52(3): 220-225].
ISSN:1976-670X
1976-6696
1976-670X
DOI:10.5483/BMBRep.2019.52.3.012