Quantitation and distribution of beta-tubulin in human cardiac myocytes.

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 of beta-tubulin protein in the right or left ventricle subjected to pressure overload, and have demonstrated that interfering with excess polymerization of beta-tubulin improves contractility. We tested the hypothesis that beta-tubulin is increased in human left ventricular hypertrophy and end-stage heart failure. Confocal microscopy of fluorescently labeled beta-tubulin protein revealed an increased density of the beta-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 beta-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 beta-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 beta-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 beta-tubulin protein contributes to cardiac dysfunction.

journal_name

J Mol Cell Cardiol

authors

Aquila-Pastir LA,DiPaola NR,Matteo RG,Smedira NG,McCarthy PM,Moravec CS

doi

10.1006/jmcc.2002.2105

keywords:

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

1513-23

issue

11

eissn

0022-2828

issn

1095-8584

pii

S002228280292105X

journal_volume

34

pub_type

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