Current Aging Science

Prof. Debomoy K. Lahiri
Department of Psychiatry Indiana University School of Medicine
Indianapolis, IN
USA

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Receptor-mediated Oxidative Stress in Murine Cerebellar Neurons is Accompanied by Phosphorylation of MAP (ERK 1/2) Kinase

Author(s): Yulia Rybakova, Evgeny Akkuratov, Konstantin Kulebyakin, Olga Brodskaya, Antonina Dizhevskaya, Alexander Boldyrev.

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.

Keywords: Carnosine, ERK 1/2, homocysteine, Na/K-ATPase, neurons, NMDA, ouabain, oxidative stress, murine cerebellar neurons, reactive oxygen species

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Article Details

VOLUME: 5
ISSUE: 3
Year: 2012
Page: [225 - 230]
Pages: 6
DOI: 10.2174/1874609811205030009
Price: $58