The Apelinergic System: Apelin, ELABELA, and APJ Action on Cell Apoptosis: Anti-Apoptotic or Pro-Apoptotic Effect?

The apelinergic system comprises two peptide ligands, apelin and ELABELA, and their cognate G-protein-coupled receptor, the apelin receptor APJ. Apelin is a peptide that was isolated from bovine stomach extracts; the distribution of the four main active forms, apelin-36, -17, -13, and pyr-apelin-13 differs between tissues. The mature form of ELABELA-32 can be transformed into forms called ELABELA-11 or -21. The biological function of the apelinergic system is multifaceted, and includes the regulation of angiogenesis, body fluid homeostasis, energy metabolism, and functioning of the cardiovascular, nervous, respiratory, digestive, and reproductive systems. This review summarises the mechanism of the apelinergic system in cell apoptosis. Depending on the cell/tissue, the apelinergic system modulates cell apoptosis by activating various signalling pathways, including phosphoinositide 3-kinase (PI3K), extracellular signal-regulated protein kinase (ERK1/2), protein kinase B (AKT), 5'AMP-activated protein kinase(AMPK), and protein kinase A (PKA). Apoptosis is critically important during various developmental processes, and any dysfunction leads to pathological conditions such as cancer, autoimmune diseases, and developmental defects. The purpose of this review is to present data that suggest a significant role of the apelinergic system as a potential agent in various therapies.