当前位置: X-MOL 学术Annu. Rev. Pharmacol. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Nanodomain Regulation of Cardiac Cyclic Nucleotide Signaling by Phosphodiesterases
Annual Review of Pharmacology and Toxicology ( IF 12.5 ) Pub Date : 2017-01-06 00:00:00 , DOI: 10.1146/annurev-pharmtox-010716-104756
Kristen Kokkonen 1 , David A. Kass 2, 3
Affiliation  

Cyclic nucleotide phosphodiesterases (PDEs) form an 11-member superfamily comprising 100 different isoforms that regulate the second messengers cyclic adenosine or guanosine 3′,5′-monophosphate (cAMP or cGMP). These PDE isoforms differ with respect to substrate selectivity and their localized control of cAMP and cGMP within nanodomains that target specific cellular pools and synthesis pathways for the cyclic nucleotides. Seven PDE family members are physiologically relevant to regulating cardiac function, disease remodeling of the heart, or both: PDE1 and PDE2, both dual-substrate (cAMP and cGMP) esterases; PDE3, PDE4, and PDE8, which principally hydrolyze cAMP; and PDE5A and PDE9A, which target cGMP. New insights regarding the different roles of PDEs in health and disease and their local signaling control are broadening the potential therapeutic utility for PDE-selective inhibitors. In this review, we discuss these PDEs, focusing on the different mechanisms by which they control cardiac function in health and disease by regulating intracellular nanodomains.

中文翻译:


磷酸二酯酶对心脏循环核苷酸信号的纳米域调节。

环状核苷酸磷酸二酯酶(PDE)形成一个11位成员的超家族,包含100个不同的同工型,这些同工型调节第二信使环状腺苷或鸟苷3',5'-单磷酸酯(cAMP或cGMP)。这些PDE同工型在底物选择性和它们对纳米域内对cAMP和cGMP的局部控制方面不同,纳米域靶向特定的细胞池和环状核苷酸的合成途径。七个PDE家族成员在生理上与调节心功能,心脏疾病重塑或两者有关:PDE1和PDE2,都是双重底物(cAMP和cGMP)酯酶; PDE1和PDE2都是双重底物(cAMP和cGMP)酯酶。PDE3,PDE4和PDE8,主要水解cAMP;以及针对cGMP的PDE5A和PDE9A。关于PDE在健康和疾病中的不同作用及其局部信号控制的新见解正在拓宽PDE选择性抑制剂的潜在治疗用途。在这篇综述中,我们将讨论这些PDE,重点关注它们通过调节细胞内纳米域来控制健康和疾病中的心脏功能的不同机制。

更新日期:2017-01-06
down
wechat
bug