Differential lipid peroxidation, mn superoxide, and bcl-2 expression contribute to the maturation-dependent vulnerability of oligodendrocytes to oxidative stress
Differential lipid peroxidation, mn superoxide, and bcl-2 expression contribute to the maturation-dependent vulnerability of oligodendrocytes to oxidative stress
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DOI：
10.1093/jnen/62.5.509
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发表时间：
2003-05-01
影响因子：
3.2
通讯作者：
Minghetti, L
中科院分区：
文献类型：
--
作者：
Bernardo, A;Greco, A;Minghetti, L
为了了解少突胶质细胞（OL）对氧化损伤的敏感性的基础上，纯化的大鼠OL培养物在不同的成熟阶段暴露于一氧化氮（NO）供体与快速或缓慢的释放动力学和叔丁基过氧化氢，膜渗透的有机氢过氧化物。OL前体（前OL）表现出最高的脆弱性，氧或氮反应物种，而成熟的OL是唯一容易受到长期持续的NO水平。细胞死亡发生坏死以及凋亡与caspase-3活性增加，只有在前OL的情况下，与抗凋亡蛋白bcl-2的表达减少。前OL也比成熟OL对脂质过氧化更敏感，如通过培养基中的F-2-异前列烷含量所测量的。最后，前OL，但不是成熟的OL，表达高水平的线粒体清除酶锰超氧化物歧化酶，这表明前OL可以有效地将阴离子超氧化物转化为过氧化氢，矛盾的是，更倾向于比成熟的OL之间的毒性不平衡过氧化氢的生产和解毒过程。这些数据表明，易受脂质过氧化作用。清除酶锰超氧化物歧化酶和抗凋亡蛋白bcl-2的表达，可能有助于成熟依赖的脆弱性的OL氧化损伤。
To understand the basis of oligodendrocyte (OL) susceptibility to oxidative injury, purified rat OL cultures at different stages of maturation were exposed to nitric oxide (NO) donors with fast or slow kinetics of release and to tert-butylhydroperoxide, a membrane-permeant organic hydroperoxide. OL precursors (pre-OL) displayed the highest vulnerability to both oxygen or nitrogen reactive species, whereas mature OLs were uniquely vulnerable to long-lasting levels of NO. Cell death occurred by necrosis as well as apoptosis associated with increased caspase-3 activity and, only in the case of pre-OLs, with a decreased expression of the anti-apoptotic protein bcl-2. Pre-OLs were also more susceptible than mature OLs to lipid peroxidation, as measured by F-2-isoprostane content in culture media. Finally, pre-OLs, but not mature OLs, expressed high levels of the mitochondrial scavenging enzyme Mn superoxide dismutase, suggesting that pre-OLs may efficiently convert anion superoxide into hydrogen peroxide and, paradoxically, be more predisposed than mature OLs to a toxic imbalance between hydrogen peroxide production and detoxification processes. These data suggest that susceptibility to lipid peroxidation. expression of the scavenging enzyme Mn superoxide dismutase and of the anti-apoptotic protein bcl-2, may contribute to the maturation-dependent vulnerability of OLs to oxidant injury.