Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas
Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas
复制标题
DOI：
10.1007/s11745-008-3197-y
复制
发表时间：
2008-10-01
期刊：
影响因子：
1.9
通讯作者：
Seyfried, Thomas N.
中科院分区：
文献类型：
--
作者：
Kiebish, Michael A.;Han, Xianlin;Seyfried, Thomas N.
长期以来，线粒体功能的改变一直被认为是癌症的标志。我们比较了C57BL/6J(B6)和Vm/DK(Vm)两个近交系小鼠非突触脑线粒体的脂质体和电子传输链的活性。VM菌株在自发性脑瘤(主要是胶质瘤)的高发率(1.5%)方面是独一无二的。VM小鼠的胶质瘤发病率是B6小鼠的约210倍。用鸟枪脂组学方法发现，Vm小鼠线粒体中乙醇胺甘油磷脂、磷脂酰丝氨酸和神经酰胺的含量高于B6小鼠，而总胆碱甘油磷脂的含量低于B6小鼠。Vm小鼠和B6小鼠的心磷脂总含量相似，但心磷脂分子种类的分布在不同品系之间有显著差异。B6非突触线粒体含有95种分子种类的心磷脂，按质量电荷分布于7个主要基团。相比之下，VM非突触线粒体只包含42种不对称分布的分子物种。Vm小鼠线粒体中复合体I、I/III和II/III酶活性低于B6小鼠，而复合体IV活性高于B6小鼠。与B6小鼠相比，Vm小鼠胶质瘤发生率高和电子传输链活性改变可能与Vm小鼠脑中线粒体脂类的异常组成有关。
Alterations in mitochondrial function have long been considered a hallmark of cancer. We compared the lipidome and electron transport chain activities of non-synaptic brain mitochondria in two inbred mouse strains, the C57BL/6J (B6) and the VM/Dk (VM). The VM strain is unique in expressing a high incidence of spontaneous brain tumors (1.5%) that are mostly gliomas. The incidence of gliomas is about 210-fold greater in VM mice than in B6 mice. Using shotgun lipidomics, we found that the mitochondrial content of ethanolamine glycerophospholipid, phosphatidylserine, and ceramide was higher, whereas the content of total choline glycerophospholipid was lower in the VM mice than in B6 mice. Total cardiolipin content was similar in the VM and the B6 mice, but the distribution of cardiolipin molecular species differed markedly between the strains. B6 non-synaptic mitochondria contained 95 molecular species of cardiolipin that were symmetrically distributed over 7 major groups based on mass charge. In contrast, VM non-synaptic mitochondria contained only 42 molecular species that were distributed asymmetrically. The activities of Complex I, I/III, and II/III enzymes were lower, whereas the activity of complex IV was higher in the mitochondria of VM mice than in B6 mice. The high glioma incidence and alterations in electron transport chain activities in VM mice compared to B6 mice could be related to the unusual composition of mitochondrial lipids in the VM mouse brain.