Adenylyl cyclase type 5 protein expression during cardiac development and stress

Che Lin Hu, Rachna Chandra, Hui Ge, Jayashree Pain, Lin Yan, Gopal Babu, Christophe Depre, Kousaku Iwatsubo, Yoshihiro Ishikawa, Junichi Sadoshima, Stephen F. Vatner, Dorothy E. Vatner

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Adenylyl cyclase (AC) types 5 and 6 (AC5 and AC6) are the two major AC isoforms expressed in the mammalian heart that mediate signals from β-adrenergic receptor stimulation. Because of the unavailability of isoform-specific antibodies, it is difficult to ascertain the expression levels of AC5 protein in the heart. Here we demonstrated the successful generation of an AC5 isoform-specific mouse monoclonal antibody and studied the expression of AC5 protein during cardiac development in different mammalian species. The specificity of the antibody was confirmed using heart and brain tissues from AC5 knockout mice and from transgenic mice overexpressing AC5. In mice, the AC5 protein was highest in the brain but was also detectable in all organs studied, including the heart, brain, lung, liver, stomach, kidney, skeletal muscle, and vascular tissues. Western blot analysis showed that AC5 was most abundant in the neonatal heart and declined to basal levels in the adult heart. AC5 protein increased in the heart with pressure-overload left ventricular hypertrophy. Thus this new AC5 antibody demonstrated that this AC isoform behaves similarly to fetal type genes, such as atrial natriuretic peptide; i.e., it declines with development and increases with pressure-overload hypertrophy.

Original languageEnglish (US)
Pages (from-to)H1776-H1782
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number5
DOIs
StatePublished - Nov 2009

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • Adenylyl cyclase isoforms
  • Hypertrophy
  • Monoclonal antibody
  • Pressure overload

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