Biomarkers of NRF2 signalling: Current status and future challenges
Christina Morgenstern,
Isabel Lastres-Becker,
Birsen Can Demirdöğen,
Vera Marisa Costa,
Andreas Daiber,
Roberta Foresti,
Roberto Motterlini,
Sibel Kalyoncu,
Burak I. Arioz,
Sermin Genc,
Monika Jakubowska,
Ioannis P. Trougakos,
Aleksandra Piechota-Polanczyk,
Michel Mickael,
Marlene Santos,
Thomas W. Kensler,
Antonio Cuadrado,
Ian M. Copple
Affiliations
Christina Morgenstern
Department of Otorhinolaryngology, Medical University of Vienna, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria; Institute of Molecular Biosciences, University of Graz, Humboldtstraße 50, A-8010, Graz, Austria
Isabel Lastres-Becker
Department of Biochemistry, School of Medicine, Universidad Autónoma de Madrid (UAM), Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas “Sols-Morreale” UAM-CSIC, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain
Birsen Can Demirdöğen
Department of Biomedical Engineering, TOBB University of Economics and Technology, Ankara, Turkey
Vera Marisa Costa
Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
Andreas Daiber
Department of Cardiology 1, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
Roberta Foresti
University Paris-Est Créteil, INSERM, IMRB, F-94010, Créteil, France
Roberto Motterlini
University Paris-Est Créteil, INSERM, IMRB, F-94010, Créteil, France
Sibel Kalyoncu
Izmir Biomedicine and Genome Center, Izmir, Turkey
Burak I. Arioz
Izmir Biomedicine and Genome Center, Izmir, Turkey; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey
Sermin Genc
Izmir Biomedicine and Genome Center, Izmir, Turkey; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey; Department of Neuroscience, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey
Monika Jakubowska
Malopolska Centre of Biotechnology, Jagiellonian University, ul. Gronostajowa 7a, 30-387, Krakow, Poland
Ioannis P. Trougakos
Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens, 15784, Greece
Aleksandra Piechota-Polanczyk
Department of Cell Cultures and Genomic Analysis, Medical University of Lodz, 90-752, Łódź, Poland
Michel Mickael
Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Postępu 36A, 05-552, Garbatka, Poland
Marlene Santos
REQUIMTE/LAQV, Escola Superior de Saúde, Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal
Thomas W. Kensler
Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA
Antonio Cuadrado
Department of Biochemistry, School of Medicine, Universidad Autónoma de Madrid (UAM), Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas “Sols-Morreale” UAM-CSIC, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain
Ian M. Copple
Department of Pharmacology & Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK; Corresponding author.
The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products. However, there is a lack of consensus regarding the most relevant set of these genes/proteins that best represents NRF2 activity across cell types and species. We present the findings of a comprehensive literature search that according to stringent criteria identifies GCLC, GCLM, HMOX1, NQO1, SRXN1 and TXNRD1 as a robust panel of markers that are directly regulated by NRF2 in multiple cell and tissue types. We assess the relevance of these markers in clinically accessible biofluids and highlight future challenges in the development and use of NRF2 biomarkers in humans.
