Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active alpha(1B)-adrenoceptors.
The regulatory function of alpha(1B)-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na(+)/K(+)-ATPase and Ca(2+)-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant alpha1B-adrenoceptor (CAMalpha(1B)-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca(2+)-ATPase (PMCA) expression was increased by 30% in CAMalpha(1B)-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2) expression. Moreover, total Ca(2+)-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na(+)/K(+)-ATPase activity nor the expression of alpha(1) and alpha(2) subunit isoforms was changed in CAMalpha(1B)-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac alpha(1B)-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.
Barreto
F
F
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brasil.
Rezende
D C
DC
Scaramello
C B V
CB
Silva
C L M
CL
Cunha
V M N
VM
Caricati-Neto
A
A
Jurkiewicz
A
A
Noël
F
F
Quintas
L E M
LE
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015854:Up-Regulation
D018340:Receptors, Adrenergic, alpha-1; D020928:Mitogen-Activated Protein Kinases; D000251:Adenosine Triphosphatases