PDE3A
Description
The PDE3A (phosphodiesterase 3A) is a protein-coding gene located on chromosome 12.
PDE3 is a phosphodiesterase belonging to a family of at least eleven related genes, each with distinct primary structure, substrate affinity, effector responses, and regulatory mechanisms. Most PDE families consist of multiple genes. PDE3 is clinically important due to its role in regulating heart muscle, vascular smooth muscle, and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals but their use is limited by arrhythmic effects and potential increase in mortality in certain applications. PDE3 enzymes regulate cardiac and vascular smooth muscle contractility. While PDE3 inhibitors were initially investigated for heart failure treatment, their use is no longer studied for this purpose due to unwanted arrhythmic side effects. However, the PDE3 inhibitor milrinone is approved for intravenous use in heart failure. Both PDE3A and PDE3B are expressed in vascular smooth muscle cells and likely modulate contraction. Their expression in vascular smooth muscle is altered under specific conditions, such as elevated cAMP and hypoxia.
PDE3A is a cyclic nucleotide phosphodiesterase that specifically targets the second messengers cAMP and cGMP, crucial regulators of various physiological processes. It also exhibits activity towards cUMP. Beyond its catalytic function, PDE3A participates in an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, leading to the dephosphorylation of SLFN12 and the activation of its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be significant in tissues with high E2 concentrations, potentially contributing to placenta remodeling.
PDE3A is also known as CGI-PDE, CGI-PDE A, CGI-PDE-A, HTNB.
