Article

Treatment with alpha-melanocyte stimulating hormone preserves calcium regulatory proteins in rat heart allografts.

Center for Preclinical Investigation, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via F.Sforza 35, Milano 20122, Italy.
Brain Behavior and Immunity (impact factor: 4.72). 09/2008; 22(6):817-23. DOI:10.1016/j.bbi.2007.11.009
Source: PubMed

ABSTRACT Prevention of graft dysfunction is a major objective in transplantation medicine. Previous research on experimental heart transplantation indicated that treatment with the immunomodulatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) improves histopathology, prolongs allograft survival, and reduces expression of the main tissue injury mediators. Because calcium-handling is critical in heart graft function, we determined the effects of transplantation injury and influences of alpha-MSH treatment on representative calcium regulatory proteins in rat heart allografts. Hearts from Brown Norway rats were transplanted heterotopically into MHC incompatible Lewis rats. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), protein kinase C epsilon (PKC epsilon), sarcoplasmic/endoplasmic reticulum calcium-ATPase 2 (SERCA2a), arrestin-beta1 (Arrb1), cholinergic receptor M2 (Chrm2), and inositol 1,4,5-triphosphate receptor 1 (InsP(3)R1) were examined in: (1) non-transplanted donor hearts; (2) allografts from saline-treated rats; and (3) allografts from rats treated with the synthetic alpha-MSH analog Nle4-DPhe7-alpha-MSH (NDP-alpha-MSH) (100 microg i.p. every 12h). Transplantation injury was associated with severe reduction in calcium regulatory protein transcription and expression level. NDP-alpha-MSH administration partly reversed inhibition of protein transcription and almost completely prevented protein loss. Finally, because certain effects of cyclic 3'-5'-adenosine monophosphate (cAMP) signaling on calcium handling in cardiac myocytes depend on activation of exchange protein directly activated by cAMP 1 (Epac1), we determined Epac1 mRNA and protein expression in heart allografts. Transplantation injury markedly reduced Epac1. NDP-alpha-MSH treatment significantly preserved both Epac1 protein and mRNA in the allografts. Administration of alpha-MSH or related melanocortins could reduce transplantation-induced dysfunction through protection of heart calcium regulatory proteins.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

calcium handling
 
calcium regulatory protein transcription
 
cardiac myocytes
 
certain effects
 
Epac1 protein
 
exchange protein
 
experimental heart transplantation
 
expression level
 
heart allografts
 
heart calcium regulatory proteins
 
heart graft function
 
main tissue injury mediators
 
protein expression
 
protein loss
 
rat heart allografts
 
representative calcium regulatory proteins
 
sarcoplasmic/endoplasmic reticulum calcium-ATPase 2
 
severe reduction
 
Transplantation injury
 
transplantation-induced dysfunction