title: Redox modulation of cellular stress response and lipoxin A4 expression by Coriolus versicolor in rat brain: Relevance to Alzheimer's disease pathogenesis.
abstract: Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is an early pathological feature in neurodegenerative diseases. As a prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a potential neurohormetic target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and lipoxin A4. Emerging interest is now focusing on molecules capable of activating the vitagene system as novel therapeutic targets to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. Mushroom-derived lipoxin A4 (LXA4) is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as rich source of polysaccharopeptides endowed with significant antitumor, antioxidant, antiviral, antibacterial and cytoprotective effects, thereby capable of stimulating host immune responses. Here we provide evidence of a neuroprotective action of the Coriolus mushroom when administered orally to rat. Expression of LXA4 was measured in different brain regions after oral administration of a Coriolus biomass preparation, given for 30 days. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, heme oxygenase-1 and thioredoxin. In the brain of rats receiving Coriolus, maximum induction of LXA4 was observed in cortex and hippocampus. Hsps induction was associated with no significant changes in IkBα, NFkB and COX-2 brain levels. Conceivably, activation of LXA4 signaling and modulation of stress-responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Trovato
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Siracusa
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Scuto
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Fronte
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Koverech
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Luca
authors.affiliation: Department of Clinical and Experimental Medicine, School of Medicine, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Serra
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Toscano
authors.affiliation: Department of Clinical and Experimental Medicine, School of Medicine, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Petralia
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy. Electronic address: calabres@unict.it.
authors.forename: V
authors.initials: V
authors.lastname: Calabrese
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003302:Coprinus / Q000737:chemistry / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D051547:Heme Oxygenase-1; D020672:I-kappa B Proteins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013879:Thioredoxins; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020672:I-kappa B Proteins; D044045:Lipoxins; C498145:Rela protein, rat; D051996:Transcription Factor RelA; C040527:lipoxin A4; D013879:Thioredoxins; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2
keywords: Alzheimer's disease; Heat shock protein70; Heme oxygenase-1; Lipoxin A4; Nutritional mushrooms; Vitagenes