ALTERATION OF THE ADRENAL ANTIOXIDANT DEFENSE SYSTEM DURING AGING IN RATS
ALTERATION OF THE ADRENAL ANTIOXIDANT DEFENSE SYSTEM DURING AGING IN RATS
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DOI：
10.1172/jci118177
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发表时间：
1995-09-01
影响因子：
15.9
通讯作者：
REAVEN, E
中科院分区：
文献类型：
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作者：
AZHAR, S;CAO, LC;REAVEN, E
本研究的目的是确定衰老对大鼠肾上腺抗氧化防御系统的影响程度，并评估该系统的任何变化对公认的与年龄相关的肾上腺皮质细胞类固醇合成能力下降的影响。这些研究是在年轻(2-5个月)和老年(12-27个月)的SD大鼠身上进行的，涉及测量类固醇合成、组织的氧化损伤、非酶抗氧化剂，如维生素C、E和谷胱甘肽，以及组织抗氧化酶(NLN和CuZN超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶)的活性和表达(mRNA、蛋白质质量和位置)。研究人员还对缺乏维生素E饮食的大鼠进行了一些测量。数据显示，幼年动物的肾上腺对氧化事件有特别好的保护；也就是说，这些肾上腺表现出最少的内源性脂质过氧化和最高水平的抗氧化剂诱导的损伤(在各种组织中测量)，并显示出极高的组织抗氧化剂水平。另一方面，衰老会导致肾上腺组织的氧化变化，通常情况下，这种变化与正常保护的抗氧化防御系统的效率降低和皮质酮的产生减少有关。我们推测，这些事件是因果相关的，即肾上腺组织氧化机制的年龄相关性降低导致对胆固醇运输至关重要的膜或胞浆因子的氧化损伤，作为这种损伤的结果，胆固醇无法到达适当的线粒体胆固醇侧链断裂位置，皮质酮的产生失败。
The goal of this study was to determine to what extent aging affects the antioxidant defense system of the rat adrenal and to evaluate the impact of any change in this system on the recognized age-related decline in steroidogenic capacity of adrenocortical cells. The studies were conducted on young (2-5 mo) and aging (12-27 mo) Sprague-Dawley rats and involved procedures measuring steroidogenesis; oxidative damage to tissue; non enzymatic antioxidants such as vitamin C, E, and glutathione; and tissue antioxidant enzyme (Nln and CuZn superoxide dismutases, catalase, and glutathione peroxidase) activity and expression (mRNA, protein mass, and location). Some measurements were made also on rats maintained on vitamin E-deficient diets. The data show that adrenals from young animals are especially well protected against oxidative events; i.e., these adrenals show the least endogenous lipid peroxidation and the highest level of resistance to prooxidant-induced damage (of various tissues measured) and show exceedingly high levels of tissue antioxidants. Aging, on the other hand, results in oxidative changes in adrenal tissue that are generally linked in time to a reduction in efficiency of the normally protective antioxidant defense system and to the decline in corticosterone production. We speculate that these events are causally related, i.e., that the age-related reduction in oxidative mechanisms in adrenal tissues leads to oxidative damage of membrane or cytosolic factors important to cholesterol transport, and, as a consequence of this damage, cholesterol cannot reach appropriate mitochondrial cholesterol side chain cleavage sites, and corticosterone production fails.