The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti-aging

被引:111
作者
Luo, Cheng [1 ]
Urgard, Egon [1 ]
Vooder, Tonu [1 ]
Metspalu, Andres [1 ,2 ]
机构
[1] Univ Tartu, Dept Biotechnol, EE-51010 Tartu, Estonia
[2] Univ Tartu, Estonian Genome Ctr, EE-50410 Tartu, Estonia
关键词
OXIDATIVE STRESS; CYCLOOXYGENASE-2; EXPRESSION; KEAP1; AGE; CHEMOPREVENTION; INHIBITION; ACTIVATION; RESOLUTION; ROFECOXIB;
D O I
10.1016/j.mehy.2011.04.002
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:174 / 178
页数:5
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