Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China ; Department of Urology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
PLoS One. 2013 Oct 3;8(10):e76731. doi: 10.1371/journal.pone.0076731. eCollection 2013.
Extracellular adenosine (ADE) interacts with cells by two pathways: by activating cell surface receptors at nanomolar/micromolar concentrations; and by interfering with the homeostasis of the intracellular nucleotide pool at millimolar concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the underlying mechanisms remain unclear. In the present study, the effects of adenosine-mediated ATP on cell viability were investigated. Adenosine treatment was found to be cytoprotective in the low intracellular ATP state, but cytotoxic under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection rely on adenosine-derived ATP formation, but not via the adenosine receptor pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP generation. These data provide a new pathway by which adenosine exerts dual biological effects on cell viability, suggesting an important role for adenosine as an ATP precursor besides the adenosine receptor pathway.
细胞外腺苷 (ADE) 通过两种途径与细胞相互作用：在纳摩尔/微摩尔浓度下激活细胞表面受体；并在毫摩尔浓度下干扰细胞内核苷酸池的内稳态。ADE 表现出细胞毒性和细胞保护作用；然而，其潜在机制尚不清楚。在本研究中，研究了腺苷介导的 ATP 对细胞活力的影响。发现腺苷处理在低细胞内 ATP 状态下具有细胞保护作用，但在正常 ATP 状态下具有细胞毒性。腺苷介导的细胞毒性和细胞保护作用依赖于由腺苷衍生的 ATP 形成，但不通过腺苷受体途径。ADE 增强了由 ATP 生成介导的蛋白酶体抑制诱导的细胞死亡。这些数据提供了一种新的途径，通过该途径，腺苷对细胞活力产生双重生物学效应，表明除了腺苷受体途径之外，腺苷作为 ATP 前体具有重要作用。
