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

Braz J Med Biol Res. 2010 May;43(5):500-5. doi: 10.1590/s0100-879x2010007500028. Epub 2010 Apr 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Calcium Signaling / physiology
  • Male
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism*
  • Myocardium / enzymology*
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Up-Regulation

Substances

  • Receptors, Adrenergic, alpha-1
  • Mitogen-Activated Protein Kinases
  • Adenosine Triphosphatases