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      Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

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          Abstract

          Redox biology is a very quickly developing area of modern biological sciences, and roles of redox homeostasis in health and disease have recently received tremendous attention. There are a range of redox pairs in the cells/tissues responsible for redox homeostasis maintenance/regulation. In general, all redox elements are interconnected and regulated by various means, including antioxidant and vitagene networks. The redox status is responsible for maintenance of cell signaling and cell stress adaptation. Physiological roles of redox homeostasis maintenance in avian species, including poultry, have received limited attention and are poorly characterized. However, for the last 5 years, this topic attracted much attention, and a range of publications covered some related aspects. In fact, transcription factor Nrf2 was shown to be a master regulator of antioxidant defenses via activation of various vitagenes and other protective molecules to maintain redox homeostasis in cells/tissues. It was shown that Nrf2 is closely related to another transcription factor, namely, NF-κB, responsible for control of inflammation; however, its roles in poultry have not yet been characterized. Therefore, the aim of this review is to describe a current view on NF-κB functioning in poultry with a specific emphasis to its nutritional modulation under various stress conditions. In particular, on the one hand, it has been shown that, in many stress conditions in poultry, NF-κB activation can lead to increased synthesis of proinflammatory cytokines leading to systemic inflammation. On the other hand, there are a range of nutrients/supplements that can downregulate NF-κB and decrease the negative consequences of stress-related disturbances in redox homeostasis. In general, vitagene–NF-κB interactions in relation to redox balance homeostasis, immunity, and gut health in poultry production await further research.

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          Most cited references394

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          Reactive oxygen species (ROS) as pleiotropic physiological signalling agents

          'Reactive oxygen species' (ROS) is an umbrella term for an array of derivatives of molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation of the different ROS leads to molecular damage, denoted as 'oxidative distress'. Here we focus on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as 'oxidative eustress'. Two species, hydrogen peroxide (H2O2) and the superoxide anion radical (O2·-), are key redox signalling agents generated under the control of growth factors and cytokines by more than 40 enzymes, prominently including NADPH oxidases and the mitochondrial electron transport chain. At the low physiological levels in the nanomolar range, H2O2 is the major agent signalling through specific protein targets, which engage in metabolic regulation and stress responses to support cellular adaptation to a changing environment and stress. In addition, several other reactive species are involved in redox signalling, for instance nitric oxide, hydrogen sulfide and oxidized lipids. Recent methodological advances permit the assessment of molecular interactions of specific ROS molecules with specific targets in redox signalling pathways. Accordingly, major advances have occurred in understanding the role of these oxidants in physiology and disease, including the nervous, cardiovascular and immune systems, skeletal muscle and metabolic regulation as well as ageing and cancer. In the past, unspecific elimination of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting disease initiation and progression in clinical trials. However, controlling specific ROS-mediated signalling pathways by selective targeting offers a perspective for a future of more refined redox medicine. This includes enzymatic defence systems such as those controlled by the stress-response transcription factors NRF2 and nuclear factor-κB, the role of trace elements such as selenium, the use of redox drugs and the modulation of environmental factors collectively known as the exposome (for example, nutrition, lifestyle and irradiation).
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            Oxidative stress, inflammation, and cancer: how are they linked?

            Extensive research during the past 2 decades has revealed the mechanism by which continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer, diabetes, and cardiovascular, neurological, and pulmonary diseases. Oxidative stress can activate a variety of transcription factors including NF-κB, AP-1, p53, HIF-1α, PPAR-γ, β-catenin/Wnt, and Nrf2. Activation of these transcription factors can lead to the expression of over 500 different genes, including those for growth factors, inflammatory cytokines, chemokines, cell cycle regulatory molecules, and anti-inflammatory molecules. How oxidative stress activates inflammatory pathways leading to transformation of a normal cell to tumor cell, tumor cell survival, proliferation, chemoresistance, radioresistance, invasion, angiogenesis, and stem cell survival is the focus of this review. Overall, observations to date suggest that oxidative stress, chronic inflammation, and cancer are closely linked. Copyright © 2010 Elsevier Inc. All rights reserved.
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              Crosstalk of reactive oxygen species and NF-κB signaling.

              NF-κB proteins are a family of transcription factors that are of central importance in inflammation and immunity. NF-κB also plays important roles in other processes, including development, cell growth and survival, and proliferation, and is involved in many pathological conditions. Reactive Oxygen Species (ROS) are created by a variety of cellular processes as part of cellular signaling events. While certain NF-κB-regulated genes play a major role in regulating the amount of ROS in the cell, ROS have various inhibitory or stimulatory roles in NF-κB signaling. Here we review the regulation of ROS levels by NF-κB targets and various ways in which ROS have been proposed to impact NF-κB signaling pathways.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                28 January 2021
                February 2021
                : 10
                : 2
                : 186
                Affiliations
                [1 ]Department of Biochemistry, Vitagene and Health Research Centre, Bristol BS4 2RS, UK
                [2 ]Department of Hygiene and Poultry Sciences, Moscow State Academy of Veterinary Medicine and Biotechnology named after K. I. Skryabin, 109472 Moscow, Russia; kochish.i@ 123456mail.ru
                [3 ]Department of Biochemistry and Physiology, Saint-Petersburg State Academy of Veterinary Medicine, 196084 St. Petersburg, Russia
                [4 ]Department of Microbiology and Biochemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
                [5 ]Department of Animal Nutrition, Faculty of Agricultural and Environmental Sciences, Szent Istvan University, H-2103 Gödöllo, Hungary
                [6 ]Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA; mkidd@ 123456uark.edu
                Author notes
                [* ]Correspondence: psurai@ 123456feedfood.co.uk
                Author information
                https://orcid.org/0000-0002-5012-8681
                Article
                antioxidants-10-00186
                10.3390/antiox10020186
                7912633
                33525511
                a14cb9da-a9c6-4636-880a-7862f47c0b81
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 December 2020
                : 25 January 2021
                Categories
                Review

                antioxidants,nf-κb,oxidative stress,poultry,redox balance
                antioxidants, nf-κb, oxidative stress, poultry, redox balance

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