Chromatin sphingomyelin changes in cell proliferation and/or apoptosis induced by ciprofibrate

Abstract

It has been shown that neutral-sphingomyelinase and sphingomyelin-synthase activities are present in chromatin and they modify the sphingomyelin (SM) content. The activity of the first enzyme is stimulated and the second inhibited, when the hepatocytes enter into the S-phase after partial hepatectomy, thus suggesting that ceramide may have a pivotal role in cell proliferation. An opposite function was attributed to ceramide in hepatocytes which undergo apoptosis after lobular ligature. In order to clarify this point, a model was developed in which the same liver cells undergo proliferation followed by induced apoptosis. To this purpose, the rats were treated for 7 days with ciprofibrate and then left without treatment for 4 days. During the treatment, the peroxisome enzyme markers increase their activity and the number of proliferating cells increases, reaching a maximum after 3 days of treatment, as shown by the number of cells positive for the proliferating cell nuclear antigen. At the same time, the chromatin sphingomyelinase activity reaches the maximum, while a similar increase is not found in the cytoplasm or in the isolated nuclei. On the contrary, SM-synthase activity is depressed in chromatin, but not in the nuclei in which a peak is shown after 3 days of ciprofibrate treatment. After drug withdrawal, the hepatocytes undergo apoptosis as confirmed by the increase of Bax and tissue transglutaminase (tTGase) expression; the chromatin SM increases as a consequence of an increase of SM-synthase activity. It can be hypothesised that chromatin SM may have a role in cell duplication by influencing the chromatin structure stability.

Differential Expressions of p53, p53R2, hRRM2 and PBR in Chronic Lymphocytic Leukemia: A Correlation with Intracellular Cholesterol

“…Earlier reports have shown the existence of cholesterol in cell nucleus of regenerating liver cells [32,33] and a presence of highly expressed cholesterol transporter, PBR, in breast cancer cells [19,34]. Our study has also shown an increased expression of PBR in nuclear fraction of lymphocytes from CLL patients as compared to control subjects (Fig.…”

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

“…In fact, during proliferation, chromatin SMS decreases whereas the one localized in the nuclear envelope increases, while an opposite profile has been observed during apoptosis. 90,91 The changes in chromatin-associated SMS might regulate accessibility of DNA for transcription by regulation of DNA associated SM, similarly to what observed in the case of double stranded RNA. 92 Surprisingly, neither SMS1 nor SMS2 localize to the nucleus and so the identities of the nuclear SMS activities remain to be established.…”

Possible Roles of Nuclear Lipids in Liver Regeneration

“…The presence of this enzyme was demonstrated both in the nuclear membrane and in the isolated chromatin (Albi et al 2003a). The activity found in the whole homogenate was 0.93 pmol/mg protein/min, in the cytosol 2.61 pmol/mg protein/min and in the nuclear membrane 0.87 pmol/mg protein/min.…”

“…No specific variations in the amounts of PI have been described during liver regeneration although it may have a role through its degradation enzymes by producing DAG (Albi et al 2003a). …”