Increase in Secretory Sphingomyelinase Activity and Specific Ceramides in the Aorta of Apolipoprotein E Knockout Mice during Aging
Increase in Secretory Sphingomyelinase Activity and Specific Ceramides in the Aorta of Apolipoprotein E Knockout Mice during Aging
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DOI：
10.1248/bpb.b13-00180
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发表时间：
2013-07-01
影响因子：
2
通讯作者：
Kikuzaki, Hiroe
中科院分区：
文献类型：
--
作者：
Kobayashi, Keiko;Nagata, Eri;Kikuzaki, Hiroe
动脉粥样硬化是由多种因素引起的，其中之一就是氧化应激。我们最近证明，全身氧化应激增加了糖尿病大鼠血浆中分泌鞘磷脂酶（sSMase）的活性并产生神经酰胺。此外，我们还发现人血浆中总神经酰胺水平与氧化低密度脂蛋白水平相关。为了研究神经酰胺种类与衰老过程中动脉粥样硬化的关系，我们比较了载脂蛋白E敲除小鼠（apoE(-/-)）和野生型小鼠（WT）神经酰胺代谢的年龄相关变化。尽管apoE（-/-）的血浆总神经酰胺水平在各年龄段均高于WT，但随着年龄的增长而下降。两株小鼠的sSMase活性在65周龄时均有所增加。当apoE（-/-）在15岁时发生动脉粥样硬化时，apoE（-/-）主动脉中C18:0、C22:0和C24:0神经酰胺水平显著升高。此外，在65 w时，C16:0和C24:1神经酰胺水平显著高于WT。这些结果表明，由于sSMase活性导致的特定神经酰胺物种水平升高有助于衰老过程中的动脉粥样硬化。
Atherosclerosis is caused by many factors, one of which is oxidative stress. We recently demonstrated that systemic oxidative stress increased secretory sphingomyelinase (sSMase) activity and generated ceramides in the plasma of diabetic rats. In addition, we also showed that the total ceramide level in human plasma correlated with the level of oxidized low-density lipoprotein. To investigate the relationship between ceramide species and atherogenesis during aging, we compared age-related changes in ceramide metabolism in apolipoprotein E knock out mice (apoE(-/-)) and wild type mice (WT). Although the total plasma ceramide level was higher in apoE(-/-) than that in WT at all ages, it decreased with increasing age. sSMase activity increased at 65 weeks (w) of age in both strains of mice. When apoE(-/-) developed atherosclerosis at 15 w of age, C18:0, C22:0, and C24:0 ceramide levels in the apoE(-/-) aorta significantly increased. Furthermore, at 65 w of age C16:0 and C24:1 ceramide levels were significantly higher than those in WT. These results suggested that elevation in levels of specific ceramide species due to sSMase activity contributed to atherogenesis during aging.