© Springer International Publishing AG 2017 213
T. Angelone et al. (eds.), Chromogranins: from Cell Biology to Physiology
and Biomedicine, UNIPA Springer Series, DOI 10.1007/978-3-319-58338-9_13
Serpinin Peptides: Tissue Distribution
and Functions
Y. Peng Loh, Niamh Cawley, Alicja Woronowicz, and Josef Troger
Abstract Serpinins are a family of peptides derived from proteolytic processing at
paired basic residues at the C-terminus of chromogranin A, followed by aminopep-
tidase activity to trim the N-terminus of the liberated peptides and pyroglutamina-
tion. Three serpinin peptides have been identified that are released from the mouse
endocrine pituitary cell line, AtT20. These include serpinin, pyroglutaminated ser-
pinin (pGlu-serpinin) and C-terminal extended serpinin, serpinin-RRG. Each of
these peptides have been found in different amounts in various tissues such as, adre-
nal 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.
Y. Peng Loh (*) • N. Cawley • A. Woronowicz
Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health, 49, Convent Drive,
Bldg. 49, Room 6A-10, Bethesda, MD 20892, USA
e-mail: [email protected]
J. Troger
Department of Ophthalmology, Medical University of Innsbruck,
Anichstraße 35, 6020 Innsbruck, Austria