Quantitation and distribution of β-tubulin in human cardiac myocytes

Louise A. Aquila-Pastir, Nicholas R. DiPaola, Jr., Rosalia G. Matteo, Nicholas G. Smedira, Patrick M. McCarthy, Christine Schomisch Moravec

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Increasing evidence suggests that derangements of cytoskeletal proteins contribute to alterations in intracellular signaling, myocyte function, and the coupling of myocytes to the extracellular matrix during cardiac hypertrophy and failure. Data from animal studies have shown an increased density β-tubulin protein in the right or left ventricle subjected to pressure overload, and have demonstrated that interfering with excess polymerization of β-tubulin improves contractility. We tested the hypothesis that β-tubulin is increased in human left ventricular hypertrophy and end-stage heart failure. Confocal microscopy of fluorescently labeled β-tubulin protein revealed an increased density of the β-tubulin network in cardiomyocytes from both hypertrophied and failing human hearts as compared to cells from nonfailing hearts. Western blot analysis on total heart homogenate showed no change in β-tubulin when data were normalized to either actin or calsequestrin, although there was a significant increase in failing human hearts when data were normalized only for a constant amount of protein per heart. The mRNA for β-tubulin was not changed in hypertrophied hearts, but was significantly decreased in failing human hearts. Thus, similar to animal models, we have shown that the density of the microtubular network within the cardiomyocyte is increased in end-stage failing human hearts. We have also shown for the first time that β-tubulin density is increased in cells from hypertrophied human hearts. Although the functional implications of this finding in the human heart remain to be explored, data from animal studies suggest that increased β-tubulin protein contributes to cardiac dysfunction.

Original languageEnglish (US)
Pages (from-to)1513-1523
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume34
Issue number11
DOIs
StatePublished - Nov 1 2002

Keywords

  • Cytoskeleton
  • Heart failure
  • Hypertrophy
  • Microtubules.
  • β-tubulin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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