Albi E, Peloso I, Magni M V
Facoltà di Medicina e Chirurgia, Università degli Studi di Perugia, Policlinico Monteluce, Perugia, 06100, Italy.
Biochem Biophys Res Commun. 1999 Sep 7;262(3):692-5. doi: 10.1006/bbrc.1999.1188.
Sphingomyelin and cholesterol play an important role in stabilising the plasma membranes architecture and in many physiological process such as cell growth and differentiation. Degradation of sphingomyelin by exogenous sphingomyelinase induces a decrease of cholesterol due either to an increase of esterification or to a reduced biosynthesis. Variations of sphingomyelin due to the presence of a neutral-sphingomyelinase and of sphingomyelin-synthase have been recently shown in rat liver nuclear membranes. The aim of this research is to study the relation between sphingomyelin and cholesterol in the nuclear membranes following sphingomyelinase activation and during cell proliferation. The nuclear membranes, isolated from liver nuclei, were analysed for their content in protein, nucleic acids, and lipids (sphingomyelin and cholesterol) before and after sphingomyelinase activation and during hepatic regeneration. The activities of nuclear membrane SM-syntase and sphingomyelinase were also determined. The results confirmed that also in the nuclear membranes sphingomyelinase, especially exogenous, causes a strong decrease in cholesterol. The increase observed of sphingomyelin during the first 18 h after hepatectomy followed by a decrease at 24 h, due to the different activity of the enzymes, is accompanied by similar behaviour of cholesterol. This confirms the effect of neutral-sphingomyelinase on cholesterol, due to an increase of esterification process. Changes in cholesterol content modify the nuclear membranes fluidity and, as consequence, mRNA transport as previously shown. It can therefore be concluded that the neutral sphingomyelinase, present in the nuclei, may, across this mechanism, regulate the cell function.
鞘磷脂和胆固醇在稳定质膜结构以及许多生理过程(如细胞生长和分化)中发挥着重要作用。外源性鞘磷脂酶对鞘磷脂的降解会导致胆固醇减少,这要么是由于酯化作用增强,要么是由于生物合成减少。最近在大鼠肝细胞核膜中发现,由于中性鞘磷脂酶和鞘磷脂合酶的存在,鞘磷脂会发生变化。本研究的目的是探讨鞘磷脂酶激活后以及细胞增殖过程中,肝细胞核膜中鞘磷脂与胆固醇之间的关系。从肝细胞核中分离出核膜,在鞘磷脂酶激活前后以及肝再生过程中,分析其蛋白质、核酸和脂质(鞘磷脂和胆固醇)含量。同时还测定了核膜鞘磷脂合成酶和鞘磷脂酶的活性。结果证实,在核膜中,鞘磷脂酶,尤其是外源性鞘磷脂酶,也会导致胆固醇显著减少。肝切除术后最初18小时内鞘磷脂增加,随后在24小时减少,这是由于酶的活性不同,胆固醇也有类似变化。这证实了中性鞘磷脂酶对胆固醇的影响,是由于酯化过程增强。如先前所示,胆固醇含量的变化会改变核膜流动性,进而影响mRNA转运。因此可以得出结论,细胞核中存在的中性鞘磷脂酶可能通过这种机制调节细胞功能。