Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active α1B-adrenoceptors
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Date
2010-05-01
Authors
Barreto, Frederico
Rezende, Daniele Campos
Scaramello, Christianne Bretas Vieira
Silva, Claudia Lucia Martins
Cunha, Valeria do Monti Nascimento
Caricati-Neto, Afonso [UNIFESP]
Jurkiewicz, Aron [UNIFESP]
Noël, Francois
Quintas, Luis Eduardo Menezes
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Abstract
The regulatory function of α1B-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 Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant α1B-adrenoceptor (CAMα1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30% in CAMα1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-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 α1 and α2 subunit isoforms was changed in CAMα1B-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 α1B-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.
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Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 43, n. 5, p. 500-505, 2010.