title: Redox signaling and histone acetylation in acute pancreatitis.
abstract: Histone acetylation via CBP/p300 coordinates the expression of proinflammatory cytokines in the activation phase of inflammation, particularly through mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and signal transducers and activators of transcription (STAT) pathways. In contrast, histone deacetylases (HDACs) and protein phosphatases are mainly involved in the attenuation phase of inflammation. The role of reactive oxygen species (ROS) in the inflammatory cascade is much more important than expected. Mitochondrial ROS act as signal-transducing molecules that trigger proinflammatory cytokine production via inflammasome-independent and inflammasome-dependent pathways. The major source of ROS in acute inflammation seems to be NADPH oxidases, whereas NF-κB, protein phosphatases, and HDACs are the major targets of ROS and redox signaling in this process. There is a cross-talk between oxidative stress and proinflammatory cytokines through serine/threonine protein phosphatases, tyrosine protein phosphatases, and MAPKs that greatly contributes to amplification of the uncontrolled inflammatory cascade and tissue injury in acute pancreatitis. Chromatin remodeling during induction of proinflammatory genes would depend primarily on phosphorylation of transcription factors and their binding to gene promoters together with recruitment of histone acetyltransferases. PP2A should be considered a key modulator of the inflammatory cascade in acute pancreatitis through the ERK/NF-κB pathway and histone acetylation.
authors.affiliation: Department of Physiology, School of Pharmacy, University of Valencia, Burjasot, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escobar
authors.forename: Javier
authors.initials: J
authors.lastname: Pereda
authors.forename: Gerardo
authors.initials: G
authors.lastname: López-Rodas
authors.forename: Juan
authors.initials: J
authors.lastname: Sastre
mesh_terms: D000107:Acetylation; D000208:Acute Disease; D000818:Animals; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010195:Pancreatitis / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D006657:Histones