Medlock K A, Merrill A H
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.
Biochem Biophys Res Commun. 1988 Nov 30;157(1):232-7. doi: 10.1016/s0006-291x(88)80037-8.
It has been hypothesized that complex sphingolipids may serve as another "lipid second messenger" system via their hydrolysis to free sphingosine, which inhibits protein kinase C and affects multiple cellular functions. To investigate sphingolipid turnover, Chinese hamster ovary cells were pulse labelled with [14C]serine and the [14C]sphingosine in cellular sphingolipids was determined over time. Much of the radiolabelled sphingosine was initially seen in ceramides and was incorporated into sphingomyelin during the 5-hour chase. A major portion of the radiolabel that was initially seen in other sphingolipids disappeared over time. Overall, about half of the total long-chain bases made during this pulse were degraded within 2 to 5 h, depending on the method of analysis. Hence, a substantial portion of the sphingosine synthesized de novo by these cells is turned over fairly quickly. Since the doubling time of these cells is 12 h, this rapid turnover may reflect the remodelling of the cell surface, or the utilization of the free sphingosine derived from sphingolipid turnover, as part of the control of cell growth and division.
据推测,复杂鞘脂类可能通过水解为游离鞘氨醇而作为另一种“脂质第二信使”系统,游离鞘氨醇可抑制蛋白激酶C并影响多种细胞功能。为了研究鞘脂类的周转,用[14C]丝氨酸对中国仓鼠卵巢细胞进行脉冲标记,并随时间测定细胞鞘脂类中[14C]鞘氨醇的含量。最初,大部分放射性标记的鞘氨醇存在于神经酰胺中,并在5小时的追踪期内掺入鞘磷脂。最初存在于其他鞘脂类中的大部分放射性标记随时间消失。总体而言,根据分析方法的不同,在此次脉冲过程中产生的总长链碱基中约有一半在2至5小时内被降解。因此,这些细胞从头合成的鞘氨醇中有很大一部分周转相当快。由于这些细胞的倍增时间为12小时,这种快速周转可能反映了细胞表面的重塑,或者作为细胞生长和分裂控制的一部分,利用了源自鞘脂类周转的游离鞘氨醇。