Vitamin C modulates AKT and CREB phosphorylation in retinal cultures via glutamate receptors and nitric oxide: Involvement in cell survival and neurite outgrowth

Background: Glutamate receptors are widely expressed in different types of cancer cells. α-Amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are ionotropic glutamate receptors which are coupled to intracellular signaling pathways that influence cancer cell survival, proliferation, and migration. Blockade of AMPA receptors by pharmacologic compounds may potentially constitute an effective tool in anticancer treatment strategies. Method: Here we investigated the impact of the AMPA receptor antagonist CFM-2 on the expression of the protein survivin, which is known to promote cancer cell survival and proliferation. We show that CFM-2 inhibits survivin expression at mRNA and protein levels and decreases the viability of cancer cells. Using a stably transfected cell line which overexpresses survivin, we demonstrate that over-expression of survivin enhances cancer cell viability and attenuates CFM-2–mediated inhibition of cancer cell growth. Result: These findings point towards suppression of survivin expression as a new mechanism contributing to anticancer effects of AMPA antagonists.

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The Nitric Oxide-Cyclic GMP Pathway Plays an Essential Role in Both Promoting Cell Survival of Cerebellar Granule Cells in Culture and Protecting the Cells Against Ethanol Neurotoxicity

Journal of Neurochemistry ◽

10.1046/j.1471-4159.1998.70051826.x ◽

2002 ◽

Vol 70 (5) ◽

pp. 1826-1838 ◽

Cited By ~ 58

Author(s):

Nicholas J. Pantazis ◽

James R. West ◽

De Dai

Keyword(s):

Nitric Oxide ◽

Cell Survival ◽

Cyclic Gmp ◽

Essential Role ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Cerebellar Granule ◽

Cells In Culture

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Role of nitric oxide and nitrosative protein damage in cigarette smoke-induced emphysematous lung damage: Attenuation by vitamin C

Nitric Oxide ◽

10.1016/j.niox.2012.04.146 ◽

2012 ◽

Vol 27 ◽

pp. S41

Author(s):

Indranil Gupta ◽

Arijit Ghosh ◽

Koustubh Panda

Keyword(s):

Nitric Oxide ◽

Vitamin C ◽

Cigarette Smoke ◽

Lung Damage ◽

Protein Damage ◽

Emphysematous Lung

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Nitric oxide and cGMP modulate retinal glutamate receptors

Journal of Neurophysiology ◽

10.1152/jn.1996.76.4.2307 ◽

1996 ◽

Vol 76 (4) ◽

pp. 2307-2315 ◽

Cited By ~ 45

Author(s):

D. G. McMahon ◽

L. V. Ponomareva

Keyword(s):

Nitric Oxide ◽

Glutamate Receptors ◽

Horizontal Cell ◽

Synaptic Function ◽

Horizontal Cells ◽

Glutamate Excitotoxicity ◽

No Donors ◽

Receptor Modulation ◽

Cell Recording ◽

Endogenous Nitric Oxide

1. In the retina, as in other regions of the vertebrate central nervous system, glutamate receptors mediate excitatory chemical synaptic transmission and are a critical site for the regulation of cellular communication. In this study, retinal horizontal cells from the hybrid less were dissociated in cell culture, voltage clamped by the whole cell recording technique, and the currents evoked by application of excitatory amino acids recorded. 2. Responses to glutamate and its agonist kainate were reduced by approximately 50% in the presence of the nitric oxide (NO) donors sodium nitroprusside and S-nitroso-N-acetylpenicillamine. The effect of these compounds was blocked by the NO scavenger hemoglobin. 3. This effect of NO donors on kainate currents could be mimicked by the application of a membrane permeable guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-Br-cGMP. The NO effect was also blocked by application of the guanylate cyclase inhibitor LY-83583, and by a protein kinase G inhibitor peptide. 4. In H1-type horizontal cells, stimulation of endogenous nitric oxide synthase with L-arginine reduced kainate responses, whereas application of D-arginine had no effect. 5. This receptor modulation mechanism may act in concert with other pre- and postsynaptic mechanisms to modify horizontal cell synaptic function according to the adaptational state of the retina and also may protect horizontal cells from glutamate excitotoxicity.

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