Activation of adenosine A3 receptors regulates vitamin C transport and redox balance in neurons.

Adenosine is an important neuromodulator in the CNS, regulating neuronal survival and synaptic transmission. The antioxidant ascorbate (the reduced form of vitamin C) is concentrated in CNS neurons through a sodium-dependent transporter named SVCT2 and participates in several CNS processes, for instance, the regulation of glutamate receptors functioning and the synthesis of neuromodulators. Here we studied the interplay between the adenosinergic system and ascorbate transport in neurons.

Dopamine-Induced Ascorbate Release From Retinal Neurons Involves Glutamate Release, Activation of AMPA/Kainate Receptors and Downstream Signaling Pathways.

Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet.

Dopamine Promotes Ascorbate Release from Retinal Neurons: Role of D Receptors and the Exchange Protein Directly Activated by cAMP type 2 (EPAC2).

Ascorbate, the reduced form of vitamin C, is highly concentrated in the central nervous system (CNS), including the retina, where it plays important physiological functions. In the CNS, the plasma membrane transporter sodium vitamin C co-transporter 2 (SVCT2) is responsible for ascorbate transport in neurons. The neurotransmitter dopamine (DA), acting through D- and D-like receptor subfamilies and classically coupled to adenylyl cyclase, is known to modulate synaptic transmission in the retina.

Dopamine promotes NMDA receptor hypofunction in the retina through D receptor-mediated Csk activation, Src inhibition and decrease of GluN2B phosphorylation.

Dopamine and glutamate are critical neurotransmitters involved in light-induced synaptic activity in the retina. In brain neurons, dopamine D receptors (DRs) and the cytosolic protein tyrosine kinase Src can, independently, modulate the behavior of NMDA-type glutamate receptors (NMDARs). Here we studied the interplay between DRs, Src and NMDARs in retinal neurons.

Nitric oxide in the nervous system: biochemical, developmental, and neurobiological aspects.

Nitric oxide (NO) is a very reactive molecule, and its short half-life would make it virtually invisible until its discovery. NO activates soluble guanylyl cyclase (sGC), increasing 3',5'-cyclic guanosine monophosphate levels to activate PKGs. Although NO triggers several phosphorylation cascades due to its ability to react with Fe II in heme-containing proteins such as sGC, it also promotes a selective posttranslational modification in cysteine residues by S-nitrosylation, impacting on protein function, stability, and allocation.

Nitric oxide regulates AKT phosphorylation and nuclear translocation in cultured retinal cells.

Previous studies have shown that nitric oxide (NO) inhibits apoptosis of retinal neurons in culture through the canonical cyclic GMP/protein kinase G (PKG)-dependent pathway, but also involving multiple kinase pathways, such as phosphatidylinositol 3' kinase (PI3k) and AKT. NO and AKT exhibit survival-promoting properties and display important roles in both CNS development and plasticity. The purpose of this study was to evaluate the effects of exogenous NO, derived from the NO donor S-nitroso-N-acetylpenicillamin (SNAP), or endogenous NO, produced from l-arginine, on AKT phosphorylation in cultured chick retinal neurons.

Nitric oxide modulates sodium vitamin C transporter 2 (SVCT-2) protein expression via protein kinase G (PKG) and nuclear factor-κB (NF-κB).

Ascorbate is an important antioxidant, which also displays important functions in neuronal tissues, including the retina. The retina is responsible for the initial steps of visual processing, which is further refined in cerebral high-order centers. The retina is also a prototypical model for studying physiologic aspects of cells that comprise the nervous system.