Although angiotensin (Ang)II-induced Janus-activated kinase (JAK)2 phosphorylation was reported to be enhanced in failing human cardiomyocytes, the downstream balance between cardio-protective (signal transducer and activator of transcription-STAT3) and the pro-inflammatory (STAT2 and STAT5) response remains unexplored. Therefore STATs phosphorylation and putative genes overexpression following JAK2 activation were investigated in isolated cardiomyocytes obtained from failing human hearts (n = 16), and from non-failing(NF) hearts of humans (putative donors, n = 6) or adult rats. In NF myocytes Ang II-induced JAK2 activation was followed by STAT3 phosphorylation (186 _ 45% at 30 min), with no STAT2 or STAT5 response. The associated B cell lymphoma (Bcl)-xL overexpression (1.05 _ 0.39 fold) was abolished by both JAK2 and extracellular signal-regulated kinase (ERK)1/2 inhibitors (AG490, 10 mM, and PD98059, 30 mM, respectively), whereas Fas ligand (Fas-L) response (0.91 _ 0.21 fold) was inhibited only by p38MAPK antagonism (SB203580, 10 mM). In failing myocytes Ang II-induced JAK2 activation was followed by STAT2 (237 _ 38%) and STAT5 (222 _ 31%) phosphorylation, with no STAT3 response. No changes in Bcl-xL expression were observed, and the associated Fas-L gene overexpression (1.14 _ 0.27 fold) being abolished by p38 mitogen-activated protein kinase (MAPK) antagonism. The altered JAK2 induced STATs response in human failing cardiomyocytes may be of relevance for the progression of cardiac dysfunction in heart failure.

Impaired JAK2-induced activation of STAT3 in failing human myocytes / G.E. Cambi; G. Lucchese; M.M. Djeokeng; A. Modesti; T. Fiaschi; G. Faggian; G. Sani; P.A. Modesti. - In: MOLECULAR BIOSYSTEMS. - ISSN 1742-206X. - STAMPA. - 8:(2012), pp. 2351-2359. [10.1039/c2mb25120e]

Impaired JAK2-induced activation of STAT3 in failing human myocytes

A. Modesti;T. Fiaschi;P. A. Modesti
2012

Abstract

Although angiotensin (Ang)II-induced Janus-activated kinase (JAK)2 phosphorylation was reported to be enhanced in failing human cardiomyocytes, the downstream balance between cardio-protective (signal transducer and activator of transcription-STAT3) and the pro-inflammatory (STAT2 and STAT5) response remains unexplored. Therefore STATs phosphorylation and putative genes overexpression following JAK2 activation were investigated in isolated cardiomyocytes obtained from failing human hearts (n = 16), and from non-failing(NF) hearts of humans (putative donors, n = 6) or adult rats. In NF myocytes Ang II-induced JAK2 activation was followed by STAT3 phosphorylation (186 _ 45% at 30 min), with no STAT2 or STAT5 response. The associated B cell lymphoma (Bcl)-xL overexpression (1.05 _ 0.39 fold) was abolished by both JAK2 and extracellular signal-regulated kinase (ERK)1/2 inhibitors (AG490, 10 mM, and PD98059, 30 mM, respectively), whereas Fas ligand (Fas-L) response (0.91 _ 0.21 fold) was inhibited only by p38MAPK antagonism (SB203580, 10 mM). In failing myocytes Ang II-induced JAK2 activation was followed by STAT2 (237 _ 38%) and STAT5 (222 _ 31%) phosphorylation, with no STAT3 response. No changes in Bcl-xL expression were observed, and the associated Fas-L gene overexpression (1.14 _ 0.27 fold) being abolished by p38 mitogen-activated protein kinase (MAPK) antagonism. The altered JAK2 induced STATs response in human failing cardiomyocytes may be of relevance for the progression of cardiac dysfunction in heart failure.
2012
8
2351
2359
G.E. Cambi; G. Lucchese; M.M. Djeokeng; A. Modesti; T. Fiaschi; G. Faggian; G. Sani; P.A. Modesti
File in questo prodotto:
File Dimensione Formato  
Impaired JAK2-induced activation.pdf

accesso aperto

Descrizione: JAK2
Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 2.42 MB
Formato Adobe PDF
2.42 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/650626
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 19
social impact