Chromogranins from Cell Biology to Physiology and Biomedicine

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et al. 2003 ) as well as in inflammatory conditions such as heart failure (Corti et al.
2000 ; Ceconi et al. 2002 ), acute coronary syndromes (Jansson et al. 2009 ), rheuma-
toid arthritis (Di Comite et  al. 2006 , 2009 ), systemic lupus erythematosis (Di
Comite et  al. 2006 ) and acute systemic inflammatory response syndrome (Zhang
et al. 2009a). It seems well established that increased plasma CGA is predictive of
shorter survival, not only in patients with metastatic neuroendocrine tumors (Arnold
et al. 2008 ; Nikou et al. 2008 ), but also in chronic heart failure (Corti et al. 2000 )
and in the critically ill, nonsurgical patients (Zhang et  al. 2008 , 2009a). Whether
plasma CGA, serves solely as passive marker of the secretory state of the various
elements of the diffuse endocrine system or, in addition, as active and functional
contributors to homeostatic regulations of normal and clinical conditions, would
depend on the ability of the prohormone and/or its derived peptides to activate or
modulate relevant cellular functions.


3 Chromogranin A Processing in Different Tissues


The natural processing of bovine CGs is well described in granules of sympathoad-
renal medullary chromaffin cells, where the resulting peptides are co-secreted with
catecholamines (Metz-Boutigue et  al. 1993 ). For the bovine sequence numerous
cleavage sites were identified. They correspond to positions 3–4, 64–65, 76–77,
78–79, 115–116, 247–248, 291–292, 315–316, 331–332, 350–351, 353–354, 358–
359, 386–387. The major generated fragments are CgA1-76 (Vasostatin-I; VS-I)
and CgA79-431 (pro-chromacin; ProChrom) (Strub et  al. 1996 ). The N-terminal
domain of CGA corresponding to vasostatin-I (VS-I) CGA1-76 is highly conserved
across vertebrates from fish to man (Turquier et al. 1999 ). Furthermore, CGA and
derived peptides were also identified in neutrophils (PMNs), in heart extracts and in


HDPs

Antimicrobial
Activities

Anti-bacterial
Anti-fungal
Anti-viral
Activities in relation with Anti-parasitic
inflammation

Vaccine adjuvant

Anti-Sepsis
Cellular
DifferentiationRegenerationTissue

Modulation
of Innate and
Adaptive
Immunity

Anti-endotoxin
ROS and NO
Production
Mast cell
Degranulation
Chemokines and
Cytokines release
Chemotactic

Leukocyte Activation


Angiogenic

Fig. 1 Biological activities of Host Defense Peptides (HDPs)


Involvement of Chromogranin A and Its Derived Peptides to Fight Infections

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