Serpinins

Role in granule biogenesis, inhibition of cell death and cardiac function

Y. P. Loh, Hisatsugu Koshimizu, N. X. Cawley, B. Tota

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4086-4092
Number of pages7
JournalCurrent Medicinal Chemistry
Volume19
Issue number24
DOIs
Publication statusPublished - 01-08-2012

Fingerprint

Cell death
Rats
Protease Nexins
Cell Death
Chromogranin A
Peptides
Endocrine System
Oxidative stress
Endocrine Cells
Neurology
Golgi Apparatus
Neurites
Transcription
Protease Inhibitors
Nervous System
Proteolysis
Neurons
Brain
Oxidative Stress
Cells

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

@article{6eb802d077a14ef7b0c3ad2e84d483d1,
title = "Serpinins: Role in granule biogenesis, inhibition of cell death and cardiac function",
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.",
author = "Loh, {Y. P.} and Hisatsugu Koshimizu and Cawley, {N. X.} and B. Tota",
year = "2012",
month = "8",
day = "1",
doi = "10.2174/092986712802429957",
language = "English",
volume = "19",
pages = "4086--4092",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "24",

}

Serpinins : Role in granule biogenesis, inhibition of cell death and cardiac function. / Loh, Y. P.; Koshimizu, Hisatsugu; Cawley, N. X.; Tota, B.

In: Current Medicinal Chemistry, Vol. 19, No. 24, 01.08.2012, p. 4086-4092.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serpinins

T2 - Role in granule biogenesis, inhibition of cell death and cardiac function

AU - Loh, Y. P.

AU - Koshimizu, Hisatsugu

AU - Cawley, N. X.

AU - Tota, B.

PY - 2012/8/1

Y1 - 2012/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84866693800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866693800&partnerID=8YFLogxK

U2 - 10.2174/092986712802429957

DO - 10.2174/092986712802429957

M3 - Article

VL - 19

SP - 4086

EP - 4092

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 24

ER -