Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9886578 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2005 | 9 Pages |
Abstract
Sphingosylphosphorylcholine (SPC) is a bioactive lipid molecule involved in a variety of cellular responses. In the present study, we demonstrated that treatment of human adipose tissue-derived mesenchymal stem cells (hATSCs) with d-erythro-SPC resulted in apoptosis-like cell death, as demonstrated by decreased cell viability, DNA strand breaks, the increase of sub-G1 fraction, cytochrome c release into cytosol, and activation of caspase-3. In contrast, the exposure of hATSCs to l-threo-SPC did not induce the cell death, suggesting that the SPC-induced cell death was selective for the d-erythro-stereoisomer of SPC. The d-erythro-SPC-induced cell death was prevented by DEVD-CHO, a caspase-3 specific inhibitor, and Z-VAD-FMK, a general caspase inhibitor, suggesting that the SPC-induced cell death of hATSCs occurs through the cytochrome c- and caspase-3-dependent pathways. In addition, d-erythro-SPC treatment stimulated the activation of mitogen-activated protein kinases, such as ERK and c-Jun NH2-terminal protein kinase (JNK), and the d-erythro-SPC-induced cell death was completely prevented by pretreatment with the MEK inhibitor, U0126, but not by pretreatment with the JNK inhibitor, SP600125, and the p38 MAPK inhibitor, SB202190, suggesting a specific involvement of ERK in the d-erythro-SPC-induced cell death. Pretreatment with U0126 attenuated the d-erythro-SPC-induced release of cytochrome c. From these results, we suggest that ERK is involved in the SPC-induced cell death of hATSC through stimulation of the cytochrome c/caspase-3-dependent pathway.
Keywords
PBSJnkc-Jun NH2-terminal protein kinaseSPCMSCsGPCRsERKDMSOG protein-coupled receptorsMAPKsMTTSphingosylphosphorylcholineAdipose tissueTUNELDimethylsulfoxideMesenchymal stem cellMesenchymal stem cellsHuman adipose tissue-derived mesenchymal stem cellsterminal deoxynucleotidyl transferase-mediated dUTP nick-end labelingPhosphate-buffered salineCell deathextracellular signal-regulated kinasemitogen-activated protein kinases
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Authors
Eun Su Jeon, Yong Jung Kang, Hae Young Song, Jae Suk Woo, Jin Sup Jung, Yong Keun Kim, Jae Ho Kim,