Journal of neurochemistry
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Journal of neurochemistry · May 2020
Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation.
Brain adenosine concentrations can reach micromolar concentrations in stressful situations such as stroke, neurodegenerative diseases or hypoxic regions of brain tumours. Adenosine can act by receptor-independent mechanism by reversing the reaction catalysed by S-adenosylhomocysteine (SAH) hydrolase, leading to SAH accumulation and inhibition of S-adenosylmethionine (SAM)-dependent methyltransferases. Astrocytes are essential in maintaining brain homeostasis but their pathological activation and uncontrolled proliferation plays a role in neurodegeneration and glioma. ⋯ Combined action of adenosine and homocysteine decreased HA proliferation by 76% ± 4%, an effect higher (p < .05) than the sum of the effects of adenosine and homocysteine alone (56% ± 5%). The inhibitory effect of adenosine on HA proliferation/viability was mimicked by two adenosine kinase inhibitors and attenuated in the presence of folate (100 µM) or SAM (50-100 µM). The results suggest that adenosine reduces HA proliferation by a receptor-independent mechanism probably involving reversal of SAH hydrolase-catalysed reaction.