127The cardiostimulation induced by Serp peptides is accompanied by an enhance-
ment of ERK1/2 and GSK3β phosphorylation (Tota et al. 2012 ). In the mammalian
heart, ERK1/2 and GSK3β, two targets of PKA phosphorylation, are components of
the RISK (reperfusion injury signalling kinase) cascade involved in myocardial pro-
tection against ischemia-reperfusion injury (Hausenloy et al. 2011 ). They presum-
ably contribute also to the anti-apoptotic effect induced by pGlu-Serp against radical
oxygen species (ROS) in cultured cerebral neurons (Koshimizu et al. 2011b). Very
recently, it was observed that pGlu-Serp reduces infarct size and preserves the
hemodynamic function of normotensive and SHR hearts, given in pre- and post-
conditioning (Pasqua et al. 2015 ; for details see Pagliaro & Penna, Chap. 11 , present
volume). In pre-conditioning, the cardioprotection elicited by the peptide is mild,
but it is streaking in post-conditioning. Administered at the reperfusion, pGlu-Serp
induced a more potent cardioprotection in SHR than in normotensive rats, as shown
by the better post-ischemic hemodynamic recovery (evaluated as LVDevP) observed
in WKY. In both SHR and WKY, the peptide also reduces contracture and the infarct
size (IS). However, the effect of pGlu-Serp on IS is less pronounced in SHR, which
show a larger area of damaged tissue. Analyses of the mechanism of action recruited
by pGlu-Serp to elicit protection showed the involvement of the RISK cascade. In
fact, co-infusion of the ischemic heart to pGlu-Serp and inhibitors of PI3K/Akt,
MitoKATP channels and PKC abolished cardioprotection (Pasqua et al. 2015 ).
5 Conclusion
On the whole, results obtained in the last 10 years of research convincingly revealed
the cardiovascular activities of the CgA-derived VSs, CST and serpinin, along with
their striking adreno-sympathetic regulatory influences. The cardiovascular role of
the CgA-derived peptides represents an important component of the finely inte-
grated local and systemic neuroendocrine networks, particularly in the presence of
a perturbed cardio circulatory homeostasis. This knowledge, which has widened the
prohormone/cytokine profile of CgA, has been paralleled and integrated by a grow-
ing number of clinical studies on the biomedical implications of both full length
protein and its derived peptides - particularly the antihypertensive CST - in various
cardiovascular diseases, in relation to their diagnostic and prognostic value (see
other chapters of the present book).
References
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Cardiac Physio-Pharmacological Aspects of Three Chromogranin A-Derived Peptides...