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Signalling pathways mediated by endothelin receptors located at the nuclear membrane
Author(s) -
MERLEN CLEMENCE,
VANIOTIS George,
VILLENEUVE Louis R,
GILLIS MarcAntoine,
CHATENET David,
FOURNIER Alain,
ALLEN Bruce G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.751.10
Endothelins (ETs) are implicated in regulating cardiac contractility and in the initiation and progression of cardiac hypertrophy. Activation of cellular signalling by the interaction of ET with its cell surface receptors (ETA and ETB) has been described. However, ETB are also located at the nucleus in cardiomyocytes. The present study was to determine the signalling pathway(s) modulated by ETB in the nuclear membrane. In fluo4/AM‐loaded adult cardiac ventricular myocytes, intracellular photolysis of a caged‐ET1 analog induced an increase in nuclear Ca2+ that was partially inhibited by the IP3 receptor inhibitor, 2‐APB. In nuclei isolated from rat heart, Gαi and Gαq co‐immunoprecipitated with ETB and incubation with ET‐1 increased Akt phosphorylation (Ser‐473) but not phospho p38 or phospho Erk1/2. Finally, the subcellular distribution of ETRs was evaluated in mice following 7 days of transverse aortic constriction (TAC)‐induced pressure overload. In sham mice, ETB was detected primarly at the nuclear membrane. An additional perinuclear staining was observed in TAC hearts. In contrast, the distribution ETA immunofluorescence was unaffected. Hence, the subcellular distribution of ETB is altered in response to chronic pressure overload. Moreover, the signalling pathways associated with ETB in the nuclear membrane appear to be different from those at the cell surface.