Abstract
Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.
Highlights
There are many systems inside a cell that can generateMitochondria are recognized as the major site for Reactive oxygen species (ROS) production (Lenaz, 2012) and both complexes I and III have been established to be the specific sites for mitochondrial ROS generation (Drose and Brandt, 2012)
Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions
This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2)
Summary
Mitochondria are recognized as the major site for ROS production (Lenaz, 2012) and both complexes I and III have been established to be the specific sites for mitochondrial ROS generation (Drose and Brandt, 2012). Many enzymes are capable of producing ROS. These include, but not limited to, NADPH oxidase (Bylund et al, 2010), xanthine oxidase (Agarwal et al, 2011), α-ketoglutarate dehydrogenase complex (Ambrus et al, 2011), d-amino acid oxidases (Fang et al, 2012), and dihydrolipoamide dehydrogenase (Zhang et al, 2011; Kareyeva et al, 2012)
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