title: Stabilization of Nrf2 by tBHQ prevents LPS-induced apoptosis in differentiated PC12 cells.
abstract: The inflammatory reaction plays an important role in the pathogenesis of the neurodegenerative disorders. tert-butylhydroquinone (tBHQ) exhibits a wide range of pharmacological activities including anti-oxidative and anti-inflammatory action. In this study, we tried to elucidate possible effects of tBHQ on lipopolysaccharide (LPS)-induced inflammatory reaction and its underlying mechanism in neuron-like PC12 cells. tBHQ inhibited LPS-induced generation of reactive oxygen species (ROS) and elevation of intracellular calcium level. It also inhibited LPS-induced cyclooxygenase 2 (COX-2), TNF-α, nuclear factor KappaB (NF-kB), and caspase-3 expression in a dose-dependent manner while stabilizing nuclear factor-erythroid 2 p45-related factor 2. Moreover, the phosphorylations of p38, ERK1/2, and JNK were suppressed by tBHQ. These results suggest that the anti-inflammatory properties of tBHQ might result from inhibition of COX-2 and TNF-α expression, inhibition of NF-kB nuclear translocation along with suppression of MAP kinases (p38, ERK1/2, and JNK) phosphorylation in PC12 cells, so may be a useful agent for prevention of inflammatory diseases.
authors: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. khodagholi@sbmu.ac.ir
authors: Fariba
authors: F
authors: Khodagholi
authors: Solaleh Khoramian
authors: SK
authors: Tusi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation; D057075:Enzyme Assays; D005978:Glutathione / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D055550:Protein Stability; D021381:Protein Transport; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006873:Hydroquinones; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C018855:2-tert-butylhydroquinone; D002374:Catalase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D005978:Glutathione