Involvement of MEK-ERK1-2 pathway in the anti-oxidant response in C6 glioma cells after diesel exhaust particles exposure. (27th May 2016)

• Record Type: Journal Article
• Authors: Farina, Francesca; Milani, Chiara; Botto, Laura; Lonati, Elena; Bulbarelli, Alessandra; Palestini, Paola
• Is Part Of: Toxicology letters. Volume 250/251(2016)
• Page Start: 57
• Page End: 65
• Publication Date: 2016-05-27
• Subjects: UFPs ultrafine particles -- CNS central nervous system -- DEP diesel exhaust particles -- PAHs polycyclic aromatic hydrocarbons -- ROS reactive oxygen species -- Nrf2 nuclear factor (erythroid-derived 2)-like 2 -- ARE antioxidant responsive elements -- HO-1 heme oxygenase-1 -- GST glutathione-S-transferase -- SOD3 superoxide dismutase 3 -- Keap1 Kelch-like ECH-associated protein 1 -- ERK1-2 extracellular signal-regulated kinase 1-2 -- PM particulate matter -- MAPKs mitogen associated protein kinases -- iNOS inducible nitric oxide kinase -- OGG1 8-oxoguanine DNA Glycosylase -- Cyp1a1 cytochrome 1a1 -- Cyp1b1 cytochrome 1b1 -- Hsp70 heat shock protein 70 -- VEGF vascular endothelial grow factor -- IL1α interleukin 1 α -- IL1β interleukin 1 β -- IL6 interleukin 6 -- TNFα tumor necrosis factor α -- MEK MAPK-ERK kinase -- CM complete medium -- SFM serum free medium -- TAC total antioxidant capacity -- GSH reduced glutathione -- AhR aryl hydrocarbon receptor -- Arnt AhR nuclear translocaor -- AP1 activator protein 1 -- NFkB nuclear factor kappa B; Diesel exhaust particles -- Oxidative stress -- ERK1-2 -- Nrf2 -- HO-1 -- Anti-oxidant proteins; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.04.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: DEP induces oxidative stress in C6glioma cells. C6glioma cells have an anti-oxidant strategy in order to regulate oxidative stress. The anti-oxidant strategy relies on the activation of MEK-ERK-1-2 pathway. 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 (25 μg/ml, DEP25, and 50 μg/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. 3 h and 24 h of DEP25 and DEP50 induced a significant increase in HO-1 levels. After 24 h, DEP25 and DEP50 induced an increase in HO-1 and Cyp1b1 levels, while increase in OGG1 level was observed only with DEP25. After 5 h 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.