The janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) pathways have been shown to play a cardioprotective role. We previously gave evidence that melanocortins afford cardioprotection in conditions of myocardial ischemia/reperfusion. Here we aimed to investigate the influence of melanocortins on the JAK/ERK/STAT signaling in cardiac and systemic responses to prolonged myocardial ischemia/reperfusion. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30 min. At the end of the 2-h reperfusion, western blot analysis of the cardioprotective transcription factors pJAK2, pERK1/2, pTyr-STAT3 and pSer-STAT3, the inflammatory mediator tumor necrosis factor-α (TNF-α), the pro-apoptotic factors BAX and c-jun N-terminal kinases (pJNK), the anti-apoptotic protein Bcl-XL, as well as of the cardioprotective enzyme heme oxygenase-1 (HO-1), was performed in the left ventricle and spleen. Intravenous treatment, during coronary artery occlusion, with the melanocortin analogs [Nle4, D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) and adrenocorticotropic hormone 1-24 [ACTH-(1-24)], induced a left ventricle up-regulation of pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in pJNK and TNF-α levels; these effects of NDP-α-MSH and ACTH-(1-24) were associated with over-expression of the pro-survival proteins HO-1 and Bcl-XL, and marked decrease of the myocardial infarct size. Melanocortin treatment did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and BAX levels. In the spleen, NDP-α-MSH and ACTH-(1-24) induced similar effects on the expression of the above transcription factors/proteins, except for pERK1/2 (down-regulated) and HO-1 (unaffected). Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-α-MSH. These results indicate that melanocortins inhibit local and systemic inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion, with consequent reduction in myocardium infarct size, seemingly via activation of the JAK/STAT signaling and with modulation of an ERK (STAT unrelated) signaling pathway.
Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion / Ottani, Alessandra; Maria, Galantucci; Ettore, Ardimento; Laura, Neri; Canalini, Fabrizio; Calevro, Anita; Zaffe, Davide; Ettore, Novellino; Paolo, Grieco; Giuliani, Daniela; Guarini, Salvatore. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - STAMPA. - 72(2013), pp. 1-8. [10.1016/j.phrs.2013.03.005]
Data di pubblicazione: | 2013 | |
Titolo: | Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion | |
Autore/i: | Ottani, Alessandra; Maria, Galantucci; Ettore, Ardimento; Laura, Neri; Canalini, Fabrizio; Calevro, Anita; Zaffe, Davide; Ettore, Novellino; Paolo, Grieco; Giuliani, Daniela; Guarini, Salvatore | |
Autore/i UNIMORE: | ||
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.phrs.2013.03.005 | |
Rivista: | ||
Volume: | 72 | |
Pagina iniziale: | 1 | |
Pagina finale: | 8 | |
Codice identificativo ISI: | WOS:000319645300001 | |
Codice identificativo Scopus: | 2-s2.0-84876952001 | |
Codice identificativo Pubmed: | 23535516 | |
Citazione: | Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion / Ottani, Alessandra; Maria, Galantucci; Ettore, Ardimento; Laura, Neri; Canalini, Fabrizio; Calevro, Anita; Zaffe, Davide; Ettore, Novellino; Paolo, Grieco; Giuliani, Daniela; Guarini, Salvatore. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - STAMPA. - 72(2013), pp. 1-8. [10.1016/j.phrs.2013.03.005] | |
Tipologia | Articolo su rivista |
File in questo prodotto:
File | Descrizione | Tipologia | |
---|---|---|---|
2013Ottani.pdf | Articolo principale | Versione dell'editore (versione pubblicata) | Administrator Richiedi una copia |
Pubblicazioni consigliate

I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris