The P2Y11–14 receptor is a double-edged regulator in stress-induced cellular senescence and aging: a narrative review

Shatat, Abdel-Aziz S.*

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

*Correspondence to: Abdel-Aziz S. Shatat, PhD, abdelaziz.said14@azhar.edu.eg.

Abstract

Cellular senescence is a process where cells reach the Hayflick number of divisions, leading to telomere dysfunction and genetic aberrations. Telomeres are bound by shelterin, preventing DNA repair proteins from accessing them, resulting in DNA damage and cellular senescence or apoptosis. Human telomerase deficiency is linked to various diseases, including aplastic anemia, dyskeratosis congenita, and early pulmonary fibrosis. Aging is characterized by a decline in cellular maintenance and repair processes, leading to the loss of hemostasis and functionality of tissues and organs over time. Purinergic receptors are essential for controlling healthy and diseased processes, activating adenosine 5′-triphosphate, and causing long-term and short-term processes. P2Y receptors, G protein coupled, have seven transmembrane-domain metabotropic receptors. Eight mammalian P2Y receptors have been cloned, with the earliest identified subtypes linked to Gq proteins, initiating the signaling pathway between phospholipase C and inositol 1,4,5-trisphosphate, and releasing Ca2+ from intracellular stores. Most interestingly, P2Y11 receptors activate and P2Y12 receptors, P2Y13 receptors, P2Y14 receptors inactivate adenylate cyclase via Gs and Gi proteins, respectively. In this review, we discuss the involvement of purinergic receptors, P2Y11, P2Y12, P2Y13 and P2Y14, in cellular senescence and aging.

P2Y11-14 受体是应激诱导细胞衰老的双刃调节器：叙述性综述

摘要

细胞衰老是指细胞达到海弗里克分裂次数，导致端粒功能障碍和基因畸变的过程。端粒被保护蛋白结合，阻止DNA修复蛋白进入端粒，导致DNA损伤和细胞衰老或凋亡。人类端粒酶缺乏症与多种疾病有关，包括再生障碍性贫血、先天性角化不良和早期肺纤维化。衰老的特征是细胞维护和修复过程的衰退，随着时间的推移导致止血功能和组织器官功能的丧失。嘌呤能受体对于控制健康和疾病过程、激活 ATP 以及导致长期和短期过程至关重要。P2Y 受体是 G 蛋白偶联受体，有七个跨膜域的代谢受体。目前已克隆了八种哺乳动物的 P2Y 受体，最早发现的亚型与 Gq 蛋白相连，启动磷脂酶 C 和 1,4,5-三磷酸肌醇之间的信号通路，并从细胞内储存释放 Ca2+。最有趣的是，P2Y11 受体通过 Gs 和 Gi 蛋白分别激活 P2Y12 受体、P2Y13 受体和 P2Y14 受体，使腺苷酸环化酶失活。这篇综述讨论了嘌呤能受体 P2Y11，P2Y12，P2Y13 和 P2Y14 参与细胞衰老和老化的情况。