Chromogranins from Cell Biology to Physiology and Biomedicine

115

SR Sarcoplasmic Reticulum
VE Vascular Endothelium
VS Vasostatin
WKY Wistar Kyoto
WT Wild-Type
β-ARs β-adrenergic receptors

1 Introduction

The finding that Chromogranin A (CgA) is a substrate for proteolytic cleavage
(Helle et al. 2007 ), and is processed to generate biologically active fragments, pro-
vided the basis for a better functional characterization of this ubiquitous endocrine
protein (Helle et  al. 2007 ). Due to the presence of multiple pairs of consecutive
dibasic and monobasic residues along the amino acid sequence (Helle et al. 2007 ),
CgA is enzymatically fragmented in several short peptides which contribute to the
endocrine/paracrine networks that regulate cell, tissue and organ function. These
fragments, which derive from either the N terminus, or the central region, or the C
terminus, are produced in a tissue-specific manner following appropriate stimuli
(Tota et al. 2014 ) (Fig.  1 ). They play a significant role in processes such as inflam-
matory and cardiovascular reactions, innate immunity, energy metabolism, and cal-
cium homeostasis, and are under examination as potential novel clinical biomarkers
(Schneider et al. 2012 ).
Within the specific cardiocirculatory context, several CgA-derived peptides
showed intriguing properties, being able to modulate cardiac and vascular func-
tion under normal conditions and in the presence of pathological alterations. This
is the case of Vasostatin (VS)-1, a potent vasodilator and cardioinhibitory agent

Chromogranin-

P P PP 431

SY ST SSS

CGA
derived
peptides

Chromostatin

124- 143 )

248- 288 )

Catestatin

344- 364 )

WE-14

316- 331 )

P

• Galactose
  Sialic acid


• 
  

Vasostatin- 1-113) (CGA347- 419 )

Vasostatin- 1-76)

A

1

S-S

P

SY ST SSS

(CGA124-- ))

Pancreastatin

(CGA248-288248-288)) (CGA344-364344-364))

WE-14

316-331)

-14

(CGA316-331)

P

PPPhosphorylation

N-acethylgalattosamine

Post-translational

modifications

347-419)

Parastatin

• 1-113) 347-419)

-1 (CGA1-76)

-2 (CGA1-113)

Chromofungin

(CGA47-66)

Serpinin

(CGA403-428)

Fig. 1 Schematic illustration of CGA processing (Modified by Tota et al. 2008 )

Cardiac Physio-Pharmacological Aspects of Three Chromogranin A-Derived Peptides...