Involvement of the ceramide signaling pathway in modulating the differentiated state of porcine thyroid cells.
Neutral sphingomyelinase (Smase) is a cell membrane-associated phospholipase that hydrolyzes sphingomyelin to phosphocholine and ceramide, a lipid second messenger involved in cell differentiation and/or apoptosis. We first evidenced that porcine cultured thyroid cells could express neutral Smase activity even if thyrotropin (TStH), an essential hormone in thyroid cell differentiation, was found to induce a 1.7-fold decrease in Smase activity. Triggering the ceramide pathway by exogenous addition of neutral bacterial Smase (0.1 U/mL for 48 h), which transiently increased ceramide level by fourfold, drastically modified thyroid cell morphology. The follicle-like structures generated by TSH were disrupted, and the Smase-induced cell spreading was accompanied by a parallel loss of cell ability to iodinate proteins as well as a decrease of the adenylate cyclase system response. These inhibitory effects have been reproduced using short-chain exogenous ceramide analogs (C2-ceramides). Overall these data showed that ceramides emerged as potential mediators of dedifferentiation in thyroid cells.
Schneider
C
C
Université de Reims Champagne-Ardenne, UFR de Médecine et de Sciences, Reims, France.
Delorme
N
N
Buisson-Legendre
N
N
Bellon
G
G
Emonard
H
H
Btaouri
H E
HE
Hornebeck
W
W
Haye
B
B
Martiny
L
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology
D002518:Ceramides; D013972:Thyrotropin; D013108:Sphingomyelin Phosphodiesterase