title: Receptor-mediated oxidative stress in murine cerebellar neurons is accompanied by phosphorylation of MAP (ERK 1/2) kinase.
abstract: A primary culture of murine cerebellar neurons was used to induce oxidative stress resulting in the accumulation of reactive oxygen species (ROS) and activation of ERK 1/2 kinase. Short-term incubation (15 min) of cerebellar neurons with homocysteine (HC) or N-methyl-D-aspartate (NMDA) induced partial ERK 1/2 phosphorylation thus providing the activation of the enzyme. Inhibitors of NMDA receptors, MK-801 or D-AP5, both prevented the activation of cells by HC or NMDA. Another receptor-dependent means of oxidative stress stimulation is exposure of cells to the cardiac glycoside ouabain, a specific inhibitor of Na/K-ATPase. Ouabain induces ROS accumulation and substantial ERK1/2 activation in neuronal cells at concentrations as low as 1 nM - 1 M, which corresponds to participation of Na/K-ATPase in intracellular signalling. Neuropeptide carnosine added to the cells 2 hours before oxidative stress prevented both ROS accumulation and ERK1/2 activation. As ERK1/2 kinase plays a key role in gene expression responsible for either cell adaptation or cell death, the model used gives a useful tool to characterize the effect of natural and synthetic anti-cancer drugs on cellular life. The data presented show that carnosine is a natural modulator of oxidative stress in neuronal cells, providing regulation of ERK1/2 activity via buffering intracellular ROS levels.
authors: International Biotechnological Center of MV Lomonosov Moscow State University, Moscow, Russia. julie_ribakova@yahoo.com
authors: Yulia
authors: Y
authors: Rybakova
authors: Evgeny
authors: E
authors: Akkuratov
authors: Konstantin
authors: K
authors: Kulebyakin
authors: Olga
authors: O
authors: Brodskaya
authors: Antonina
authors: A
authors: Dizhevskaya
authors: Alexander
authors: A
authors: Boldyrev
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006710:Homocysteine / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D061251:Primary Cell Culture; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; D010042:Ouabain; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D002336:Carnosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000254:Sodium-Potassium-Exchanging ATPase