The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti-aging
The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti-aging
复制标题
DOI：
10.1016/j.mehy.2011.04.002
复制
发表时间：
2011-08-01
影响因子：
4.7
通讯作者：
Metspalu, Andres
中科院分区：
文献类型：
--
作者：
Luo, Cheng;Urgard, Egon;Metspalu, Andres
氧化应激和炎症是许多慢性疾病及其并发症的常见特征，并且与致癌作用有关。环氧合酶2（COX - 2）是前列腺素合成的一种限速酶，在生理学和病理学中都起着重要作用，但在科学界和临床界一直存在争议。然而，近期的研究表明，核因子红细胞2相关因子2（Nrf2）对氧化应激具有保护作用。此外，已证明依赖COX - 2的亲电氧化衍生物（EFOX）分子可通过激活依赖Nrf2的抗氧化反应元件（ARE）充当抗炎介质。这些研究使人们对COX - 2介导的事件有了更深入的了解。所有组织，尤其是上皮组织和内皮组织的功能会随着年龄的增长而下降，从而导致活性氧物质（ROS）的产生。在大多数组织中，COX - 2的表达随着年龄的增长而增加，部分原因是ROS、化学反应、物理剪切力以及饮食分子。在此我们讨论与COX - 2炎症和抗炎反应相关的新发现。综上所述，我们假设在衰老过程中COX - 2水平会升高，因为ROS水平的升高需要依赖COX - 2的EFOX参与抗炎以及Nrf2/ARE信号传导进行抗氧化。我们还提出，由于COX - 2在平衡炎症和抗炎反应中的作用，它可能作为一种内在的生物衰老时钟。（C）2011爱思唯尔有限公司。保留所有权利。
Oxidative stress and inflammation are constant features of many chronic diseases and complications, and have been linked to carcinogenesis. Cyclooxygenase 2 (COX-2), a rate-limiting enzyme for the synthesis of prostaglandins, plays important roles in physiology and pathology, but has been a source of controversy within the scientific and clinical community. However, recent work has shown that nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against oxidative stress. Furthermore, COX-2-dependent electrophile oxo-derivative (EFOX) molecules have been shown to act as anti-inflammatory mediators via activation of the Nrf2-dependent antioxidant response element (ARE). These studies have provided more insight into COX-2-mediated events. The function of all tissues, especially epithelial and endothelial tissues, declines with age, leading to the production of reactive oxygen species (ROS). COX-2 expression increases with aging in most tissues, due in part to ROS, chemical reactions, physical shearing, and dietary molecules. Here we discuss new findings related to COX-2 inflammatory and anti-inflammatory responses. Taken together, we hypothesize that COX-2 levels increase during the aging process because increasing levels of ROSs necessitate the involvement of COX-2-dependent EFOXs for anti-inflammation and Nrf2/ARE signaling for antioxidation. We also propose that COX-2 may act as an intrinsic biological aging clock due to its role in balancing inflammatory and anti-inflammatory responses. (C) 2011 Elsevier Ltd. All rights reserved.