Extracellular Degradation Into Adenosine and the Activities of Adenosine Kinase and AMPK Mediate Extracellular NAD+ -Produced Increases in the Adenylate Pool of BV2 Microglia Under Basal Conditions

Frontiers in Cellular Neuroscience
Jie ZhangWeihai Ying

Abstract

Cumulating evidence has indicated NAD+ deficiency as a common central pathological factor of multiple diseases and aging. NAD+ supplement is highly protective in various disease and aging models, while two key questions have remained unanswered: (1) Does extracellular NAD+ also produce its effects through its degradation product adenosine? (2) Does extracellular NAD+ produce the protective effects by affecting cells under pathological insults only, or by affecting both normal cell and the cells under pathological insults? Since extracellular NAD+ can be degraded into adenosine, and endogenous adenosine levels are in the nanomolar range under physiological conditions, extracellular NAD+ may produce its effects through its degradation into adenosine. In this study we used BV2 microglia as a cellular model to test our hypothesis that NAD+ treatment can increase the intracellular adenylate pool under basal conditions through its extracellular degradation into adenosine. Our study has shown that extracellular NAD+ is degraded into adenosine extracellularly, which enters BV2 microglia through equilibrative nucleoside transporters under basal conditions. The intracellular adenosine is converted to AMP by adenosine kinase, which increa...Continue Reading

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Citations

Feb 6, 2020·International Journal of Molecular Sciences·Kornkamon LertsuwanJomnarong Lertsuwan
May 20, 2020·Antioxidants·Nady BraidySam van Eeden
Mar 24, 2021·Cellular and Molecular Life Sciences : CMLS·Massimiliano GasparriniNadia Raffaelli
Apr 20, 2021·Molecular Nutrition & Food Research·Karen Alejandra Méndez-LaraJosep Julve

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