TY - JOUR
T1 - Left ventricular phosphorylation patterns of Akt and ERK1/2 after triiodothyronine intracoronary perfusion in isolated hearts and short-term in vivo treatment in Wistar rats
AU - Morales, José A.
AU - López, Ruth M.
AU - López, Jorge S.
AU - Lozano, Jair
AU - Jarillo, Rosa A.
AU - Flores, Héctor
AU - Castillo, Enrique F.
N1 - Publisher Copyright:
© 2020 Mashhad University of Medical Sciences. All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - Objective(s): To determine the effects of triiodothyronine (T3) intracoronary perfusion in isolated hearts and short-term administration in rats on the left ventricular (LV) phosphorylation patterns of Akt and ERK1/2. Materials and Methods: Cardiodynamic and hemodynamic parameters were evaluated in Langendorff-perfused hearts. Left ventricles were used for histomorphometric and Western blot analyses. Short-term hyperthyroidism was established by T3 (500 μg.kg-1.d-1; subcutaneous injection) for 1 (T31d), 3 (T33d), and 10 (T310d) days. Results: Isolated hearts receiving T3 perfusion did not modify LV developed pressure, +dP/dtmax, -dP/ dtmin, heart rate, and coronary perfusion pressure compared with vehicle-perfused hearts. P-ERK1/2 and p-Akt levels in LV tissues after 5, 15, or 60 min of T3 or vehicle perfusion were similar. Compared with their time-matched controls, isolated hearts of T33d and T310d rats exhibited LV hypertrophy and increased absolute values of +dP/dtmax and -dP/dtmin (i.e., positive inotropic and lusitropic effects). P-ERK1/2 decreased in LV tissues of T31d and T310d but not in those of T33d rats, and p-Akt levels augmented in left ventricles of T33d and stayed unaltered in those of T31d and T310d rats. Conclusion: T3 intracoronary perfusion did not alter cardiodynamics and hemodynamics nor influence the activation of Akt and ERK of normal hearts. Accordingly, the rapid non-genomic effects of T3 were not evident. Short-term T3 treatment provoked cardiac hypertrophy coincidental with increased LV function and associated with transient Akt activation and cyclic ERK1/2 inhibition; which implies activation of physiological hypertrophy signaling and deactivation of pathological hypertrophy signaling, respectively.
AB - Objective(s): To determine the effects of triiodothyronine (T3) intracoronary perfusion in isolated hearts and short-term administration in rats on the left ventricular (LV) phosphorylation patterns of Akt and ERK1/2. Materials and Methods: Cardiodynamic and hemodynamic parameters were evaluated in Langendorff-perfused hearts. Left ventricles were used for histomorphometric and Western blot analyses. Short-term hyperthyroidism was established by T3 (500 μg.kg-1.d-1; subcutaneous injection) for 1 (T31d), 3 (T33d), and 10 (T310d) days. Results: Isolated hearts receiving T3 perfusion did not modify LV developed pressure, +dP/dtmax, -dP/ dtmin, heart rate, and coronary perfusion pressure compared with vehicle-perfused hearts. P-ERK1/2 and p-Akt levels in LV tissues after 5, 15, or 60 min of T3 or vehicle perfusion were similar. Compared with their time-matched controls, isolated hearts of T33d and T310d rats exhibited LV hypertrophy and increased absolute values of +dP/dtmax and -dP/dtmin (i.e., positive inotropic and lusitropic effects). P-ERK1/2 decreased in LV tissues of T31d and T310d but not in those of T33d rats, and p-Akt levels augmented in left ventricles of T33d and stayed unaltered in those of T31d and T310d rats. Conclusion: T3 intracoronary perfusion did not alter cardiodynamics and hemodynamics nor influence the activation of Akt and ERK of normal hearts. Accordingly, the rapid non-genomic effects of T3 were not evident. Short-term T3 treatment provoked cardiac hypertrophy coincidental with increased LV function and associated with transient Akt activation and cyclic ERK1/2 inhibition; which implies activation of physiological hypertrophy signaling and deactivation of pathological hypertrophy signaling, respectively.
KW - Akt
KW - ERK1-2
KW - Heart hypertrophy
KW - Rat
KW - Triiodothyronine treatment
UR - http://www.scopus.com/inward/record.url?scp=85089713655&partnerID=8YFLogxK
U2 - 10.22038/IJBMS.2020.44776.10451
DO - 10.22038/IJBMS.2020.44776.10451
M3 - Artículo
AN - SCOPUS:85089713655
SN - 2008-3866
VL - 23
SP - 1091
EP - 1099
JO - Iranian Journal of Basic Medical Sciences
JF - Iranian Journal of Basic Medical Sciences
IS - 8
ER -