Role of MEK-ERK pathway in sphingosylphosphorylcholine-induced cell death in human adipose tissue-derived mesenchymal stem cells

• Published in: Biochimica et biophysica acta Vol. 1734; no. 1; pp. 25 - 33
• Main Authors: Jeon, Eun Su, Kang, Yong Jung, Song, Hae Young, Woo, Jae Suk, Jung, Jin Sup, Kim, Yong Keun, Kim, Jae Ho
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-05-2005
• Subjects: Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - metabolism; Caspase 3; Caspases - metabolism; Cell death; Cell Death - drug effects; Cells, Cultured; Cytochromes c - metabolism; ERK; Humans; MAP Kinase Signaling System - drug effects; Mesenchymal stem cell; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - pharmacology; Protein Kinase Inhibitors - pharmacology; Protein-Serine-Threonine Kinases - metabolism; SPC; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Stem Cells - cytology; Stem Cells - metabolism; PBS; Mesenchymal stem cell; Adipose tissue; DMSO; JNK; SPC; MTT; MSCs; TUNEL; Cell death; GPCRs; hATSCs; MAPKs; ERK
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2005.01.005

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 NH
2-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.