The role of AMPK in metabolism and its influence on DNA damage repair
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REVIEW
The role of AMPK in metabolism and its influence on DNA damage repair Michał Szewczuk1 · Karolina Boguszewska1 · Julia Kaźmierczak‑Barańska1 · Bolesław T. Karwowski1 Received: 27 May 2020 / Accepted: 5 October 2020 © The Author(s) 2020
Abstract One of the most complex health disproportions in the human body is the metabolic syndrome (MetS). It can result in serious health consequences such as type 2 diabetes mellitus, atherosclerosis or insulin resistance. The center of energy regulation in human is AMP-activated protein kinase (AMPK), which modulates cells’ metabolic pathways and protects them against negative effects of metabolic stress, e.g. reactive oxygen species. Moreover, recent studies show the relationship between the AMPK activity and the regulation of DNA damage repair such as base excision repair (BER) system, which is presented in relation to the influence of MetS on human genome. Hence, AMPK is studied not only in the field of counteracting MetS but also prevention of genetic alterations and cancer development. Through understanding AMPK pathways and its role in cells with damaged DNA it might be possible to improve cell’s repair processes and develop new therapies. This review presents AMPK role in eukaryotic cells and focuses on the relationship between AMPK activity and the regulation of BER system through its main component—8-oxoguanine glycosylase (OGG1). Keywords AMPK · DNA damage · DNA repair · 8-oxoguanine glycosylase
Introduction The MetS (metabolic syndrome) is a combination of specific systemic symptoms associated with improperly functioning metabolic pathways, failures of energy utilization and energy storage mechanisms. Hypertension, hyperglycemia, central obesity and low level of serum high-density lipoprotein are main characteristics [1]. It is assumed that MetS-related diseases, as well as MetS itself, result from unhealthy dietary habits and in some extent from genetic predispositions. The more advanced the state of disease development is, the more complex the treatment approach and lifestyle changes have * Michał Szewczuk [email protected] * Bolesław T. Karwowski [email protected] Karolina Boguszewska [email protected] Julia Kaźmierczak‑Barańska julia.kazmierczak‑[email protected] 1
DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, Ul. Muszynskiego 1, 90‑151 Lodz, Poland
to be. MetS and accompanying diseases increase patient’s risk of further health problems, including many types of cancer [2]. MetS is also associated with oxidative stress, ROS (reactive oxygen species) generation and inflammation in many organs, therefore it is one of factors causing DNA damage [1–3]. T2DM (type 2 diabetes mellitus) has become one of the most common human health problems with around 422 million cases among adults worldwide. It is estimated, that the global prevalence will increase by 55% up to the year 2035 [4]. A crucial role in T2DM is played by IR (insulin resistance). Re
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