Title:Serpinins: Role in Granule Biogenesis, Inhibition of Cell Death and Cardiac Function
VOLUME: 19 ISSUE: 24
Author(s):Y. P. Loh, H. Koshimizu, N. X. Cawley and B. Tota
Affiliation:National Institutes of Health, Bldg. 49, Room 5A22, Bethesda, Md. 20892, USA.
Keywords:Chromogranin A, serpinin, pGlu-serpinin, granule biogenesis, neuroprotection, myocardial contractility, Preconditioning, Reperfusion injury, Vasostatin, Cardiac.
Abstract:Serpinins are a family of peptides derived from proteolytic cleavage of the penultimate and the last pair of basic residues at the
C-terminus of Chromogranin A. Three forms of naturally occurring serpinin have been found in AtT-20 pituitary cells and rat heart. They
are serpinin, pyrogutaminated (pGlu) -serpinin and a C-terminally extended form, serpinin-RRG. In addition pGlu-serpinin has been
found in brain, primarily in neurites and nerve terminals and shown to have protective effects against oxidative stress on neurons and
pituitary cells. Serpinin has also been demonstrated to regulate granule biogenesis in endocrine cells by up-regulating the protease
inhibitor, protease nexin-1 transcription via a cAMP-PKA-sp1 pathway. This leads to inhibition of granule protein degradation in the
Golgi complex which in turn promotes granule formation. More recently, pGlu-serpinin has been demonstrated to enhance both
myocardial contractility (inotropy) and relaxation (lusitropy). In the Langendorff perfused rat heart, pGlu-serpinin showed a
concentration-dependent positive inotropic effect exerted through a cAMP-PKA dependent pathway. In conclusion, the serpinin peptides
have profound effects at many levels that affect the endocrine and nervous systems and cardiac function.
