Adenosine decreases oxidative stress and protects H2O2‑treated neural stem cells against apoptosis through decreasing Mst1 expression

Abstract

Abstract. Overproduction of free radicals during oxidative stress induces damage to key biomolecules and activates programed cell death pathways. Neuronal cell death in the nervous system leads to a number of neurodegenerative diseases. The aim of the present study was to evaluate the neuroprotective effect of adenosine on inhibition of apoptosis induced by hydrogen peroxide (H 2 O 2 ) in bone marrow-derived neural stem cells (B-dNSCs), with focus on its regulatory effect on the expression of mammalian sterile 20-like kinase 1 (Mst1), as a novel proapoptotic kinase. B-dNSCs were exposed to adenosine at different doses (2, 4, 6, 8 and 10 µM) for 48 h followed by 125 µM H 2 O 2 for 30 min. Using MTT, terminal deoxynucleotidyl transferase dUTP nick-end labeling and real-time reverse transcription polymerase chain reaction assays, the effects of adenosine on cell survival, apoptosis and Mst1, nuclear factor (erythroid-derived 2)-like 2 and B-cell lymphoma 2 and adenosine A1 receptor expression were evaluated in pretreated B-dNSCs compared with controls (cells treated with H 2 O 2 only). Firstly, results of the MTT assay indicated 6 µM adenosine to be the most protective dose in terms of promotion of cell viability. Subsequent assays using this dosage indicated that apoptosis rate and Mst1 expression in B-dNSCs pretreated with 6 µM adenosine were significantly decreased compared with the control group. These findings suggest that adenosine protects B-dNSCs against oxidative stress-induced cell death, and therefore, that it may be used to promote the survival rate of B-dNSCs and as a candidate for the treatment of oxidative stress-mediated neurological diseases.

Adenosine Improves Mitochondrial Function and Biogenesis in Friedreich’s Ataxia Fibroblasts Following L-Buthionine Sulfoximine-Induced Oxidative Stress

“…Various pharmacological agents and natural products targeting oxidative stress [ 45 , 46 , 47 , 48 , 49 , 50 , 51 ] have been considered in the management of neuromuscular disorders, including FRDA [ 38 , 52 , 53 ]. Adenosine and its derivatives have been reported to exhibit free radical scavenging activities [ 54 ] and protect bone marrow-derived neural stem cells against hydrogen peroxide (H 2 O 2 )-induced oxidative stress and apoptosis [ 55 ].…”

Metabonomics Study on Naotaifang Extract Alleviating Neuronal Apoptosis after Cerebral Ischemia-Reperfusion Injury

“…The results showed that endogenous adenosine concentration increased significantly, which was positively correlated with local blood-oxygen supply [ 21 ]. In addition, Gholinejad et al found that adenosine could reduce oxidative stress by inhibiting Mst1 expression and protect neural stem cells treated with H 2 O 2 from apoptosis [ 22 ]. Inosine is a natural nucleoside derived from the degradation of adenosine, which is initially thought to have no biological effect.…”

Phylogenetic conservation of the interdependent homeostatic relationship of sleep regulation and redox metabolism

“…In addition, increased orexin A/hypocretin 1 peptide causes mitochondrial impairment and dysfunction, contributing to increased cellular ROS (Li et al 2020 ). Lastly, adenosine alleviates oxidative stress by increasing expression levels of an essential antioxidant gene, nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) (Gholinejad et al 2018 ), suggesting that adenosine and oxidative burden could act together to drive sleep and bring redox balance back to homeostatic levels.…”