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

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Portugal, CC (Author) Other; da Encarnacao, TG (Author) Other; Sagrillo, MA (Author) Other; Pereira, MR (Author) Other; Relvas, JB (Author) FMUP; Socodato, R (Author) Other; Paes de Carvalho, R (Author) Other

Journal

Title: Free Radical Biology and Medicine

Vol. 163

Pages: 43-55

ISSN: 0891-5849

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-00T-7HZ

DOI: 10.1016/j.freeradbiomed.2020.11.039

Abstract (EN): 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. We found that selective activation of A3, but not of A1 or A2a, adenosine receptors modulated ascorbate transport, decreasing intracellular ascorbate content. Fodrster resonance energy transfer (FRET) analyses showed that A3 receptors associate with the ascorbate transporter SVCT2, suggesting tight signaling compartmentalization between A3 receptors and SVCT2. The activation of A3 receptors increased ascorbate release in an SVCT2-dependent manner, which largely altered the neuronal redox status without interfering with cell death, glycolytic metabolism, and bioenergetics. Overall, by regulating vitamin C transport, the adenosinergic system (via activation of A3 receptors) can regulate ascorbate bioavailability and control the redox balance in neurons.

Language: English

Type (Professor's evaluation): Dissemination

No. of pages: 13