Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
Department of Neurosurgery, New Jersey Medical School, Rutgers University, Newark, NJ 07102, USA.
Neurochem Int. 2021 Jul;147:105054. doi: 10.1016/j.neuint.2021.105054. Epub 2021 May 5.
Adenosine kinase (ADK) is the key regulator of adenosine and catalyzes the metabolism of adenosine to 5'-adenosine monophosphate. The enzyme exists in two isoforms: a long isoform (ADK-long, ADK-L) and a short isoform (ADK-short, ADK-S). The two isoforms are developmentally regulated and are differentially expressed in distinct subcellular compartments with ADK-L localized in the nucleus and ADK-S localized in the cytoplasm. The nuclear localization of ADK-L and its biochemical link to the transmethylation pathway suggest a specific role for gene regulation via epigenetic mechanisms. Recent evidence reveals an adenosine receptor-independent role of ADK in determining the global methylation status of DNA and thereby contributing to epigenomic regulation. Here we summarize recent progress in understanding the biochemical interactions between adenosine metabolism by ADK-L and epigenetic modifications linked to transmethylation reactions. This review will provide a comprehensive overview of ADK-associated changes in DNA methylation in developmental, as well as in pathological conditions including brain injury, epilepsy, vascular diseases, cancer, and diabetes. Challenges in investigating the epigenetic role of ADK for therapeutic gains are briefly discussed.
腺苷激酶 (ADK) 是调节腺苷代谢的关键酶，可催化腺苷转化为 5'-单磷酸腺苷。该酶有两种同工型：长型 (ADK-long，ADK-L) 和短型 (ADK-short，ADK-S)。两种同工型受发育调控，并在不同的亚细胞区室中差异表达，ADK-L 定位于核内，ADK-S 定位于细胞质。ADK-L 的核定位及其与转甲基化途径的生化联系提示其通过表观遗传机制参与基因调控的特定作用。最近的证据揭示了 ADK 在决定 DNA 整体甲基化状态方面的一种独立于腺苷受体的作用，从而有助于表观基因组调控。本文总结了 ADK-L 介导的腺苷代谢与转甲基化反应相关的表观遗传修饰之间的生化相互作用的最新进展。本文将全面概述 ADK 相关的 DNA 甲基化变化在发育过程中的作用，以及在脑损伤、癫痫、血管疾病、癌症和糖尿病等病理条件下的作用。简要讨论了研究 ADK 对表观遗传作用以获得治疗效果的挑战。
