[60]Fullerene derivative modulates adenosine and metabotropic glutamate receptors gene expression: a possible protective effect against hypoxia

Abstract

BackgroundGlutamate, the main excitatory neurotransmitter, is involved in learning and memory processes but at higher concentration results excitotoxic causing degeneration and neuronal death. Adenosine is a nucleoside that exhibit neuroprotective effects by modulating of glutamate release. Hypoxic and related oxidative conditions, in which adenosine and metabotropic glutamate receptors are involved, have been demonstrated to contribute to neurodegenerative processes occurring in certain human pathologies.ResultsHuman neuroblastoma cells (SH-SY5Y) were used to evaluate the long time (24, 48 and 72 hours) effects of a [60]fullerene hydrosoluble derivative (t3ss) as potential inhibitor of hypoxic insult. Low oxygen concentration (5% O2) caused cell death, which was avoided by t3ss exposure in a concentration dependent manner. In addition, gene expression analysis by real time PCR of adenosine A1, A2A and A2B and metabotropic glutamate 1 and 5 receptors revealed that t3ss significantly increased A1 and mGlu1 expression in hypoxic conditions. Moreover, t3ss prevented the hypoxia-induced increase in A2A mRNA expression.ConclusionsAs t3ss causes overexpression of adenosine A1 and metabotropic glutamate receptors which have been shown to be neuroprotective, our results point to a radical scavenger protective effect of t3ss through the enhancement of these neuroprotective receptors expression. Therefore, the utility of these nanoparticles as therapeutic target to avoid degeneration and cell death of neurodegenerative diseases is suggested.

[60]Fullerene derivative modulates adenosine and metabotropic glutamate receptors gene expression: a possible protective effect against hypoxia

“…Thus, the effect of t3ss derivative on the modulation of mGlu 1 gene expression could be hypothetically related to the one reported for mGlu 1 antagonists, which reduce the damage in post ischemic conditions [36]. The herein proposed possible modulatory effect of t3ss on NMDA receptors, and consequently on Ca 2+ homeostasis could be related to the modulation of the expression of metabotropic glutamate receptor belonging to group I [37]. Both mechanisms of action of t3ss could thus lead to the protective effect observed during MTT viability assay, acting both synergically or independently one from the other.…”

Modulation of Adenosine Receptors and Antioxidative Effect of Beer Extracts in in Vitro Models

“…Adenosine regulates neuroplasticity, cognitive and motor function, and emotion behaviors and it is related to many cerebral dysfunctions in human diseases [30,31]. Additionally, adenosine receptors function and level have been involved in neuroprotective and antitumoral mechanisms in C6 [32,33,34,35,36,37] and SH-SY5Y cells [32,38,39,40,41].…”

Influence of C60 Fullerenes on the Mechanokinetic and Biochemical Parameters of Muscle Soleus Contraction in Chronically Alcoholised Rats with Experimentally-Induced Ischemia

“…Водорозчинні фуллерени C 60 проявляють захисний ефект за нейродеґенерації різноманітної етіології, зокрема спостерігається значне зростання толерантности нервової тканини до гіпоксії через вплив на гени, які відповідальні за збільшення експресії глутаматних метаботропних рецепторів та аденозину [14,15]. Це достатньо важливо, адже одним з головних аспектів ефективного відновлення функціонування скелетного м'яза після ішемічного пошкодження є збереження стану нерва, що іннервує м'яз.…”