Influence of L-carnitine on CD95 cross-lining-induced apoptosis and ceramide generation in human cell lines: correlation with its effects on purified acidic and neutral sphingomyelinases in vitro.
Recently, we examined the effects of a short-term (5-days) intravenous L-carnitine (6 g/die) treatment on apoptosis of CD4 and CD8 cells from 10 AIDS patients. Without inducing side effects, L-carnitine administration has been shown to induce a potent reduction in the percentage of cells undergoing apoptosis, paralleled by a significant increase of CD4 an CD8 cells. Interestingly, L-carnitine treatment led to a significant reduction of peripheral blood mononuclear cell-associated ceramide (an intracellular messenger for apoptosis) that correlated with the decrease of apoptotic CD4- and CD8-positive cells. These results suggest that L-carnitine could be an effective antiapoptotic drug use with AIDS patients. In this article we report the results of in vitro studies performed to better characterize the effects of L-carnitine on cell apoptosis. Previously, a high expression of the Fas (CD95/APO-1)/Fas ligand system in peripheral blood mononuclear cells from HIV-positive individuals has been reported and could be responsible for the observed relevant apoptosis of both infected and uninfected cells. Thus, we investigated the in vitro effects of L-carnitine on CD95 cross-linking-induced apoptosis through an anti-CD95 mAb in Fas-sensitive cell lines (HuT78 and U937). The results strongly support the in vivo observations. Our data indicate that L-carnitine is able to inhibit CD95-induced apoptosis of these cells, most likely by preventing sphingomyelin breakdown and consequent ceramide synthesis. The effect of L-carnitine seems to be specific for acidic sphingomyelinase as shown by experiments performed in vitro and using purified neutral or acidic sphingomyelinases.
Di Marzio
L
L
Department of Experimental Medicine, University of L'Aquila, Italy.
Alesse
E
E
Roncaioli
P
P
Muzi
P
P
Moretti
S
S
Marcellini
S
S
Amicosante
G
G
De Simone
C
C
Cifone
M G
MG
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D017209:Apoptosis / Q000187:drug effects*; D002331:Carnitine / Q000494:pharmacology*; D002460:Cell Line; D002518:Ceramides / Q000096:biosynthesis*; D003432:Cross-Linking Reagents; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D019014:fas Receptor / Q000378:metabolism*
D002518:Ceramides; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D019014:fas Receptor; D013108:Sphingomyelin Phosphodiesterase; D002331:Carnitine