Serpinin Peptides: Tissue Distribution and Functions

Abstract

Serpinins are a family of peptides derived from proteolytic processing at paired basic residues at the C-terminus of chromogranin A, followed by aminopeptidase activity to trim the N-terminus of the liberated peptides and pyroglutamination. Three serpinin peptides have been identified that are released from the mouse endocrine pituitary cell line, AtT20. These include serpinin, pyroglutaminated serpinin (pGlu-serpinin) and C-terminal extended serpinin, serpinin-RRG. Each of these peptides have been found in different amounts in various tissues such as, adrenal medulla, heart, retina and brain. Cellular localization and secretion studies of these peptides indicate that they are packaged in secretory granules and secreted in a regulated (stimulated) manner and therefore function extracellularly as signaling molecules. Serpinin and pGlu-serpinin play an important role in up-regulating secretory granule biogenesis in endocrine cells. In the heart, endocrine cells and neurons, serpinin and pGlu-serpinin have been found to protect these cells against cell death under oxidative or ischemic stress. Serpinin and pGlu-serpinin are also positive cardiac β-adrenergic-like inotropes with a powerful effect on enhancing myocardial contractility. Additionally, serpinin, pGlu-serpinin and serpinin-RRG have been shown to have anti-angiogenesis effects with the C-terminal extended peptide being the most potent. The many functions of the serpinin peptides indicate their physiological importance.