Suppression of steroidogenesis and activator protein-1 transcription factor activity in rat adrenals by vitamin E deficiency-induced chronic oxidative stress
Suppression of steroidogenesis and activator protein-1 transcription factor activity in rat adrenals by vitamin E deficiency-induced chronic oxidative stress
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DOI：
10.1016/j.jnutbio.2003.11.007
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发表时间：
2004-04-01
影响因子：
5.6
通讯作者：
Azhar, S
中科院分区：
文献类型：
--
作者：
Abidi, P;Leers-Sucheta, S;Azhar, S
过度的氧化应激和相关的大分子损伤被认为是衰老的关键特征，并且似乎有助于肾上腺和睾丸间质细胞中类固醇激素产生的年龄相关下降。目前的研究是为了研究衰老过程中过度氧化应激降低氧化反应转录因子激活蛋白- l的功能表达的潜在机制，通过维持维生素E缺乏的大鼠组6个月，在体内诱导慢性氧化应激。缺乏维生素e的动物的血浆、肝脏和肾上腺组织中这种维生素的含量可以忽略不计，并且对体外脂质过氧化反应非常敏感。在维生素e缺乏大鼠制备的肾上腺皮质细胞中，促肾上腺皮质激素（ACTH）、二丁基camp或20 α -羟胆固醇的合成和分泌在体外显著降低，AP-1 dna结合活性在维生素e缺乏大鼠的肾上腺提取物中降低了55%，而SP-1的结合活性没有相应的变化。维生素E缺乏介导的AP-1活性的丧失不是由于组成蛋白的二聚体组成的改变，而是由于Fos和Jun蛋白家族成员的稳态水平的普遍下调。有趣的是，维生素E缺乏也降低了氧化还原调节的Ref-1蛋白的表达。总的来说，这些数据表明，慢性氧化应激特异性下调AP-1转录因子复合物的基本成分，并表明AP-1表达的异常可能对细胞内胆固醇运输和类固醇激素产生的关键过程产生不利影响。(C) 2004爱思唯尔公司版权所有。
Excessive oxidative stress and associated macromolecular damage are considered to be key features of aging, and appear to contribute to the age-related decline in steroid hormone production in adrenal and testicular Leydig cells. The current studies were initiated to examine the potential mechanism by which excessive oxidative stress during aging attenuates the functional expression of the oxidant-responsive transcription factor Activator protein-L Chronic oxidative stress was induced in vivo by maintaining groups of rats on a diet deficient in vitamin E for 6 months. Plasma, liver, and adrenal tissues from vitamin E-deficient animals had negligible levels of this vitamin and showed high susceptibility to in vitro lipid peroxidation. Synthesis and secretion of corticosterone in response to corticotropin (ACTH), dibutyryl-cAMP, or 20alpha-hydroxycholesterol in vitro was significantly reduced in adrenocortical cells prepared cells from rats deficient in vitamin E. AP-1 DNA-binding activity was diminished similar to55 % in adrenal extracts from vitamin E-deficient rats with no corresponding change in the binding activity of SP-1. The vitamin E deficiency-mediated loss of AP-1 activity was not due to an alteration in the dimeric composition of constituent proteins, but rather to a general down-regulation of steady-state levels of members of the Fos and Jun families of proteins. Interestingly, vitamin E deficiency also reduced the expression of the redox-regulated Ref-1 protein. Collectively these data demonstrate that chronic oxidative stress specifically down-regulates essential components of the AP-1 transcription factor complex, and suggest that aberrancies in AP-1 expression may adversely affect processes crucial for intracellular cholesterol transport and steroid hormone production. (C) 2004 Elsevier Inc. All rights reserved.