Adenovirus-mediated gene transfer reconstitutes depressed sarcoplasmic reticulum Ca2+-ATPase levels and shortens prolonged cardiac myocyte Ca2+ transients

Frank J. Giordano, Huaping He, Patrick McDonough, Markus Meyer, M. Richard Sayen, Wolfgang H. Dillmann

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Background: Decreased expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase of the cardiac myocyte (SERCA2) and abnormal Ca2+ regulation have been independently linked to human heart failure. This study was designed to determine whether expression of a SERCA2 transgene could reconstitute depressed cardiac myocyte SERCA2 levels, augment SR Ca2+ uptake, and shorten prolonged excitation-contraction (EC)-associated Ca2+ transients in neonatal rat cardiac myocytes (NM). Methods and Results: Cultured NM were treated with phorbol-12-myristate-13-acetate (PMA), a compound that decreases endogenous SERCA2 expression and results in prolongation of EC-assocIated Ca2+ transients. PMA-treated NM had a 75% reduction in SERCA2 mRNA and a 40% reduction in SERCA2 protein levels. SERCA2 adenovirus infection increased SERCA2 mRNA expression to 2.5 times control and reconstituted SERCA2 protein levels in PMA-treated cells. This reconstitution was associated with a 32.4% reduction in the time for decline of the Indo-1 Ca2+ transient to half-maximum levels (t( 1/4 )) [Ca2+](i)) (P<.05). A 34.5% augmentation of oxalate-facilitated SR Ca2+ uptake was also documented in SERCA2 adenovirus-infected cells (P<.05). Conclusions: Adenovirus-mediated expression of a SERCA2 transgene can reconstitute depressed endogenous SERCA2 levels, shorten prolonged Ca2+ transients, and augment SR Ca2+ uptake. It is conceivable that such an approach might be used in vivo to normalize altered Ca2+ regulation in human heart failure.

Original languageEnglish (US)
Pages (from-to)400-403
Number of pages4
JournalCirculation
Volume96
Issue number2
DOIs
StatePublished - Jul 15 1997
Externally publishedYes

Keywords

  • Adenovirus
  • Calcium
  • Cell
  • Genes
  • Molecular biology
  • Myocytes

Fingerprint Dive into the research topics of 'Adenovirus-mediated gene transfer reconstitutes depressed sarcoplasmic reticulum Ca<sup>2+</sup>-ATPase levels and shortens prolonged cardiac myocyte Ca<sup>2+</sup> transients'. Together they form a unique fingerprint.

Cite this