Albi Elisabetta, Perrella Giuseppina, Lazzarini Andrea, Cataldi Samuela, Lazzarini Remo, Floridi Alessandro, Ambesi-Impiombato Francesco Saverio, Curcio Francesco
Laboratory of Nuclear Lipid BioPathology, Research Center of Biochemical-Specialized Analyses, Perugia 06100, Italy.
Department of Clinical and Biological Sciences, University of Udine, Udine 33100, Italy.
Int J Mol Sci. 2014 Jun 27;15(7):11555-65. doi: 10.3390/ijms150711555.
Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein.
增殖的甲状腺细胞比静止细胞对紫外线-C辐射更敏感。这种效应是由核磷脂酰胆碱和鞘磷脂代谢介导的。已证明质子束可阻止细胞生长并刺激细胞凋亡，但迄今为止，文献中尚无关于其可能作用机制的迹象。在此，我们研究了质子对培养的FRTL-5细胞的影响。我们发现，质子束在静止细胞中轻微刺激核中性鞘磷脂酶活性并抑制核鞘磷脂合酶活性，而在增殖细胞中强烈刺激核中性鞘磷脂酶活性且不改变核鞘磷脂合酶活性。对中性鞘磷脂酶/鞘磷脂合酶比值（细胞功能状态的标志物）的研究表明，如果细胞是静止的，质子束会使FRTL-5细胞处于促凋亡状态；如果细胞是增殖的，则处于初始凋亡状态。细胞生命的变化伴随着核鞘磷脂的减少和bax蛋白的增加。
