EVIDENCE OF OXIDATIVE STRESS IN VERY LONG CHAIN FATTY ACID - TREATED OLIGODENDROCYTES AND POTENTIALIZATION OF ROS PRODUCTION USING RNA INTERFERENCE-DIRECTED KNOCKDOWN OF ABCD1 AND ACOX1 PEROXISOMAL PROTEINS
EVIDENCE OF OXIDATIVE STRESS IN VERY LONG CHAIN FATTY ACID - TREATED OLIGODENDROCYTES AND POTENTIALIZATION OF ROS PRODUCTION USING RNA INTERFERENCE-DIRECTED KNOCKDOWN OF ABCD1 AND ACOX1 PEROXISOMAL PROTEINS
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DOI：
10.1016/j.neuroscience.2012.03.058
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发表时间：
2012-06-28
期刊：
影响因子：
3.3
通讯作者：
Lizard, G.
中科院分区：
文献类型：
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作者：
Baarine, M.;Andreoletti, P.;Lizard, G.
X-连锁肾上腺脑白质营养不良(X-ALD)和假性新生儿肾上腺脑白质营养不良(P-NALD)分别是由于过氧化物体型三磷酸腺苷结合盒转运体D(ABCD1)功能丧失和单一过氧化物体酶缺乏症(ACOX1：ACOX1)引起的神经退行性脱髓鞘疾病。由于这些蛋白质参与超长链脂肪酸(VLCFA：C24：0，C26：0)的分解代谢，X-ALD和P-NALD患者的特点是VLCFA在血浆和组织中积聚。由于过氧化物酶体参与了活性氧(ROS)和氮(RNS)的代谢，我们检测了VLCFA对表达或不表达ABCD1或Acox1的158N小鼠少突胶质细胞氧化状态的影响。VLCFA引发氧化应激，其特征是ROS和RNS的过量产生与脂质过氧化、蛋白质羰化、超氧化物歧化酶(SOD)活性升高、过氧化氢酶活性和谷胱甘肽水平降低有关。即使在没有VLCFA的情况下，ABCD1或Acox1的siRNA敲除也会增加ROS和RNS的产生，尤其是可能增加VLCFA诱导的ROS的过量产生。此外，主要是在Acox1水平降低的细胞中，VLCFA和中性脂的水平在未处理和VLCFA处理的细胞中都显著增加。我们在158N小鼠少突胶质细胞上的数据强调了VLCFA诱导氧化应激，并证明ABCD1或Acox1基因敲除有助于破坏氧化还原平衡，支持氧化应激与ABCD1或Acox1过氧化体蛋白缺乏之间的联系。(C)2012年IBRO。爱思唯尔有限公司出版。保留所有权利。
X-linked adrenoleukodystrophy (X-ALD) and pseudo neonatal adrenoleukodystrophy (P-NALD) are neurodegenerative demyelinating diseases resulting from the functional loss of the peroxisomal ATP-binding cassette transporter D (ABCD1) and from single peroxisomal enzyme deficiency (Acyl-CoA oxidase1: ACOX1), respectively. As these proteins are involved in the catabolism of very long chain fatty acids (VLCFA: C24:0, C26:0), X-ALD and P-NALD patients are characterized by the accumulation of VLCFA in plasma and tissues. Since peroxisomes are involved in the metabolism of reactive oxygen species (ROS) and nitrogen species (RNS), we examined the impact of VLCFA on the oxidative status of 158N murine oligodendrocytes expressing or not Abcd1 or Acox1. VLCFA triggers an oxidative stress characterized by an overproduction of ROS and RNS associated with lipid peroxidation, protein carbonylation, increased superoxide dismutase (SOD) activity, decreased catalase activity and glutathione level. SiRNA knockdown of Abcd1 or Acox1 increased ROS and RNS production even in the absence of VLCFA, and especially potentialized VLCFA-induced ROS overproduction. Moreover, mainly in cells with reduced Acox1 level, the levels of VLCFA and neutral lipids were strongly enhanced both in untreated and VLCFA - treated cells. Our data obtained on 158N murine oligodendrocytes highlight that VLCFA induce an oxidative stress, and demonstrate that Abcd1 or Acox1 knockdown contributes to disrupt RedOx equilibrium supporting a link between oxidative stress and the deficiency of Abcd1 or Acox1 peroxisomal proteins. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.