title: Involvement of MEK-ERK1-2 pathway in the anti-oxidant response in C6 glioma cells after diesel exhaust particles exposure.
abstract: Ultrafine particles translocate to the central nervous system and activate oxidative stress-related pathways. The transcription factor Nrf2 activation by ERK1-2 has been suggested as a key regulator of cellular response to oxidative stress. C6 glioma cells have been treated with different doses of diesel exhaust particles (25μg/ml, DEP25, and 50μg/ml, DEP50), for different times. Cells have been screened for oxidative stress and inflammatory markers, and for the activation of the MEK-ERK1-2 pathway. The same markers have been examined after inhibition of MEK, the kinase upstream to ERK1-2. 3h and 24h of DEP25 and DEP50 induced a significant increase in HO-1 levels. After 24h, DEP25 and DEP50 induced an increase in HO-1 and Cyp1b1 levels, while increase in OGG1 level was observed only with DEP25. After 5h of treatment with DEP25, ERK1-2 resulted phosphorylated, concomitantly with a significant increase in HO-1 levels, no changes in iNOS levels, and decreased levels of anti-oxidant enzymes. After treatment with MEK inhibitor U0126, ERK1-2 showed no activation, with a consequent decrease in Nrf2, no increase in HO-1 and a significant increase of iNOS. MEK inhibitor is able to deplete anti-oxidant enzymes. In conclusion, the MEK-ERK1-2 pathway is involved in regulating the anti-oxidant strategies to compensate the oxidative status induced by DEP treatment.
authors.affiliation: Department of Medicine and Surgery, Polaris Centre, University of Milano-Bicocca, Monza, Italy; NeuroMi, Milan Center of Neuroscience, Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. Electronic address: francesca.farina@hotmail.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Farina
authors.affiliation: Department of Medicine and Surgery, Polaris Centre, University of Milano-Bicocca, Monza, Italy; NeuroMi, Milan Center of Neuroscience, Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Milani
authors.affiliation: Department of Medicine and Surgery, Polaris Centre, University of Milano-Bicocca, Monza, Italy; NeuroMi, Milan Center of Neuroscience, Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Botto
authors.affiliation: Department of Medicine and Surgery, Polaris Centre, University of Milano-Bicocca, Monza, Italy; NeuroMi, Milan Center of Neuroscience, Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Lonati
authors.affiliation: Department of Medicine and Surgery, Polaris Centre, University of Milano-Bicocca, Monza, Italy; NeuroMi, Milan Center of Neuroscience, Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bulbarelli
authors.affiliation: Department of Medicine and Surgery, Polaris Centre, University of Milano-Bicocca, Monza, Italy; NeuroMi, Milan Center of Neuroscience, Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Palestini
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D052638:Particulate Matter; D047428:Protein Kinase Inhibitors; D001335:Vehicle Emissions; C585499:Cyp1b1 protein, rat; D065633:Cytochrome P-450 CYP1B1; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D045647:DNA Glycosylases; C483741:OGG1 protein, rat
keywords: Anti-oxidant proteins; Diesel exhaust particles; ERK1-2; HO-1; Nrf2; Oxidative stress