Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls.
Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls.
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脂质过氧化衍生羰基化合物的氧化与还原代谢。
DOI：
10.1016/j.cbi.2014.12.028
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发表时间：
2015-06-05
影响因子：
5.1
通讯作者：
Bhatnagar, Aruni
中科院分区：
文献类型：
--
作者：
Singh, Mahavir;Kapoor, Aniruddh;Bhatnagar, Aruni
广泛的研究表明，活性氧（ROS）的产生增加导致各种病理条件下的组织损伤和慢性退行性疾病。虽然ROS是高度反应性的，可以引起显著的损伤，但膜和脂蛋白中的多不饱和脂质是它们的主要目标。ROS引发的脂质过氧化反应产生一系列反应性羰基物质（RCS），这些RCS传播和放大ROS相关的损伤。氧化脂质中产生的几种RCS，如4-羟基反式-2-壬烯醛（HNE）、4-氧代-2-（E）-壬烯醛（ONE）、丙烯醛、丙二醛（MDA）和磷脂醛，已显示在氧化应激条件下产生，并通过消耗谷胱甘肽和其他还原剂导致蛋白质、脂质和DNA修饰而导致组织损伤和功能障碍。为了防止组织损伤，这些RCS被几种氧化还原酶代谢，包括醛酮还原酶（AKR）超家族的成员、醛脱氢酶（ALDH）和醇脱氢酶（ADH）。通过这些酶的代谢导致RCS失活和解毒，尽管在某些条件下，它也可以导致产生触发适应性反应的信号分子。RCS通过氧化还原酶的代谢转化和解毒防止了不加选择的ROS毒性，同时保留了ROS信号传导。更好地了解RCS代谢的氧化还原酶可能会导致新的治疗干预措施的发展，以减少氧化损伤的几种疾病状态，并提高抵抗ROS诱导的毒性。
Extensive research has shown that increased production of reactive oxygen species (ROS) results in tissue injury under a variety of pathological conditions and chronic degenerative diseases. While ROS are highly reactive and can incite significant injury, polyunsaturated lipids in membranes and lipoproteins are their main targets. ROS-triggered lipid peroxidation reactions generate a range of reactive carbonyl species (RCS), and these RCS spread and amplify ROS-related injury. Several RCS generated in oxidizing lipids, such as 4-hydroxy trans-2-nonenal (HNE), 4-oxo-2-(E)-nonenal (ONE), acrolein, malondialdehyde (MDA) and phospholipid aldehydes have been shown to be produced under conditions of oxidative stress and contribute to tissue injury and dysfunction by depleting glutathione and other reductants leading to the modification of proteins, lipids, and DNA. To prevent tissue injury, these RCS are metabolized by several oxidoreductases, including members of the aldo-keto reductase (AKR) superfamily, aldehyde dehydrogenases (ALDHs), and alcohol dehydrogenases (ADHs). Metabolism via these enzymes results in RCS inactivation and detoxification, although under some conditions, it can also lead to the generation of signaling molecules that trigger adaptive responses. Metabolic transformation and detoxification of RCS by oxidoreductases prevent indiscriminate ROS toxicity, while at the same time, preserving ROS signaling. A better understanding of RCS metabolism by oxidoreductases could lead to the development of novel therapeutic interventions to decrease oxidative injury in several disease states and to enhance resistance to ROS-induced toxicity.
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ALDH3A1介导的细胞保护针对4-羟基-2-非纳尔的分子机制。
影响因子：
7.4
作者：
Black, William;Chen, Ying;Matsumoto, Akiko;Thompson, David C.;Lassen, Natalie;Pappa, Aglaia;Vasiliou, Vasilis
通讯作者：
Vasiliou, Vasilis
影响因子：
20.1
作者：
BHATNAGAR, A
通讯作者：
BHATNAGAR, A
影响因子：
4.1
作者：
BEEDLE, AS;REES, HH;GOODWIN, TW
通讯作者：
GOODWIN, TW
影响因子：
4.4
作者：
Choudhary, S;Xiao, TL;Ansari, NH
通讯作者：
Ansari, NH
影响因子：
4.4
作者：
Davis, Janine;Davis, Dionne;Piatigorsky, Joram
通讯作者：
Piatigorsky, Joram