Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress
Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress
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DOI：
10.1111/j.1474-9726.2008.00395.x
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发表时间：
2008-08-01
期刊：
影响因子：
7.8
通讯作者：
Sanchez, Diego
中科院分区：
文献类型：
--
作者：
Ganfornina, Maria D.;Do Carmo, Sonia;Sanchez, Diego
许多神经系统病理与载脂蛋白D（ApoD）水平升高有关，载脂蛋白D是一种脂运载蛋白，也在正常发育和衰老期间表达。果蝇中的ApoD同源基因Glial Lazarillo调节衰老大脑中的应激抗性和神经变性。在这里，我们首次研究了ApoD在脊椎动物模式生物中的保护潜力。小鼠ApoD功能的丧失增加了对氧化应激的敏感性和脑脂质过氧化水平，并损害运动和学习能力。人ApoD在小鼠脑中的过表达产生相反的作用，增加存活率并防止氧化剂处理后脑脂质过氧化物的升高。这些观察结果，连同其在氧化损伤后在脑中的转录上调，将ApoD鉴定为具有保护性的急性反应蛋白，因此通过控制过氧化脂质介导的有益功能。
Many nervous system pathologies are associated with increased levels of apolipoprotein D (ApoD), a lipocalin also expressed during normal development and aging. An ApoD homologous gene in Drosophila, Glial Lazarillo, regulates resistance to stress, and neurodegeneration in the aging brain. Here we study for the first time the protective potential of ApoD in a vertebrate model organism. Loss of mouse ApoD function increases the sensitivity to oxidative stress and the levels of brain lipid peroxidation, and impairs locomotor and learning abilities. Human ApoD overexpression in the mouse brain produces opposite effects, increasing survival and preventing the raise of brain lipid peroxides after oxidant treatment. These observations, together with its transcriptional up-regulation in the brain upon oxidative insult, identify ApoD as an acute response protein with a protective and therefore beneficial function mediated by the control of peroxidated lipids.