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  • Title: 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.
    Author: Di Marzio L, Alesse E, Roncaioli P, Muzi P, Moretti S, Marcellini S, Amicosante G, De Simone C, Cifone MG.
    Journal: Proc Assoc Am Physicians; 1997 Mar; 109(2):154-63. PubMed ID: 9069584.
    Abstract:
    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.
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