title: Antioxidant responses and cellular adjustments to oxidative stress.
abstract: Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases.
authors.affiliation: Department of Cell Biology and Immunology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Espinosa-Diez
authors.affiliation: Department of Cell Biology and Immunology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Miguel
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Aapistie 7, University of Oulu, FI-90230 Oulu, Finland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mennerich
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Aapistie 7, University of Oulu, FI-90230 Oulu, Finland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kietzmann
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM) and Departamento de Biología Molecular, Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain; Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sánchez-Pérez
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM) and Departamento de Biología Molecular, Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain; Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Cadenas
authors.affiliation: Department of Cell Biology and Immunology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Nicolás Cabrera 1, 28049 Madrid, Spain. Electronic address: slamas@cbm.csic.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Lamas
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D018808:Transcription Factor AP-1; D054464:Peroxiredoxins; D005978:Glutathione
keywords: Antioxidants; ER stress; Ischemia–reperfusion; Redox signaling; Transcription factors