Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University, 00161 Rome, Italy.
Department of Biology and Biotechnology "C. Darwin", Sapienza University, 00185 Rome, Italy.
Int J Mol Sci. 2021 Mar 5;22(5):2593. doi: 10.3390/ijms22052593.
3'-5' cyclic nucleotide phosphodiesterases (PDEs) are a large family of enzymes playing a fundamental role in the control of intracellular levels of cAMP and cGMP. Emerging evidence suggested an important role of phosphodiesterases in heart formation, but little is known about the expression of phosphodiesterases during cardiac development. In the present study, the pattern of expression and enzymatic activity of phosphodiesterases was investigated at different stages of heart formation. C57BL/6 mice were mated and embryos were collected from 14.5 to 18.5 days of development. Data obtained by qRT-PCR and Western blot analysis showed that seven different isoforms are expressed during heart development, and PDE1C, PDE2A, PDE4D, PDE5A and PDE8A are modulated from E14.5 to E18.5. In heart homogenates, the total cAMP and cGMP hydrolytic activity is constant at the evaluated times, and PDE4 accounts for the majority of the cAMP hydrolyzing ability and PDE2A accounts for cGMP hydrolysis. This study showed that a subset of PDEs is expressed in developing mice heart and some of them are modulated to maintain constant nucleotide phosphodiesterase activity in embryonic and fetal heart.
3'-5' 环核苷酸磷酸二酯酶 (PDEs) 是一个大家族的酶，在控制细胞内 cAMP 和 cGMP 水平方面发挥着重要作用。新出现的证据表明磷酸二酯酶在心脏形成中起着重要作用，但关于磷酸二酯酶在心脏发育过程中的表达知之甚少。在本研究中，研究了不同心脏形成阶段磷酸二酯酶的表达模式和酶活性。将 C57BL/6 小鼠交配，并从发育的 14.5 天到 18.5 天收集胚胎。通过 qRT-PCR 和 Western blot 分析获得的数据表明，在心脏发育过程中有七种不同的同工酶表达，并且 PDE1C、PDE2A、PDE4D、PDE5A 和 PDE8A 从 E14.5 到 E18.5 进行调节。在心脏匀浆中，在评估的时间内总 cAMP 和 cGMP 水解活性保持不变，PDE4 占大部分 cAMP 水解能力，PDE2A 占 cGMP 水解。本研究表明，一组 PDEs 在发育中的小鼠心脏中表达，其中一些被调节以维持胚胎和胎儿心脏中核苷酸磷酸二酯酶活性的恒定。
