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Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver Regeneration
Laboratory of Nuclear Lipid BioPathology, Research Center of Biochemical-Specialized Analyses, 06100 Perugia, Italy
Department of Clinical and Biological Sciences, University of Udine, 33100 Udine, Italy
* Author to whom correspondence should be addressed.
Received: 7 December 2012; in revised form: 24 January 2013 / Accepted: 26 February 2013 / Published: 25 March 2013
Abstract: Nuclear sphingomyelin is a key molecule for cell proliferation. This molecule is organized with cholesterol and proteins to form specific lipid microdomains bound to the inner nuclear membrane where RNA is synthesized. Here, we have reported the ability of the sphingomyelin present in the nuclear microdomain to bind DNA and regulate its synthesis, and to highlight its role in cell proliferation induced by partial hepatectomy. During G1/S transition of the cell cycle, sphingomyelin and DNA content is very high and it is strongly reduced after exogenous sphingomyelinase treatment. During the S-phase of the cell cycle, the stimulation of sphingomyelinase and inhibition of sphingomyelin–synthase are accompanied by the DNA synthesis start. To assess the specificity of the results, experiments were repeated with trifluoperazine, a drug known to affect the synthesis of lipids and DNA and to stimulate sphingomyelinase activity. The activity of sphingomyelinase is stimulated in the first hour after hepatectomy and sphingomyelin–DNA synthesis is strongly attenuated. It may be hypothesized that the nuclear microdomain represents a specific area of the inner nuclear membrane that acts as an active site of chromatin anchorage thanks to the stabilizing action of sphingomyelin. Thus, sphingomyelin metabolism in nuclear lipid microdomains is suggested to regulate cell proliferation.
Keywords: nucleus; nuclear lipid microdomains; sphingomyelin; sphingomyelinase; sphingomyelin–synthase; cell proliferation
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Cite This Article
MDPI and ACS Style
Albi, E.; Lazzarini, A.; Lazzarini, R.; Floridi, A.; Damaskopoulou, E.; Curcio, F.; Cataldi, S. Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver Regeneration. Int. J. Mol. Sci. 2013, 14, 6529-6541.
Albi E, Lazzarini A, Lazzarini R, Floridi A, Damaskopoulou E, Curcio F, Cataldi S. Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver Regeneration. International Journal of Molecular Sciences. 2013; 14(4):6529-6541.
Albi, Elisabetta; Lazzarini, Andrea; Lazzarini, Remo; Floridi, Alessandro; Damaskopoulou, Eleni; Curcio, Francesco; Cataldi, Samuela. 2013. "Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver Regeneration." Int. J. Mol. Sci. 14, no. 4: 6529-6541.