Contractile activity and passive stretch regulate tubulin mrna and
protein content in cardiac myocytes: implications for contractile
dysfunction in vivo.
Watson, Peter A., Ross Hannan, Lois L. Carl, and Kathyrn E. Giger.
Weis Center for Research, Geisinger Clinic, 100 North Academy
Avenue, Danville, PA 17822-2615
APStracts 3:0075C, 1996.
Accumulation of tubulin protein and an increased array of microtubules
has been associated with contractile dysfunction in cardiac myocytes
following pressure overload in vivo. Experiments were performed to
assess the ability of mechanical stimuli experienced by ventricular
cardiac myocytes during the progression of hypertrophic and dilated
pathology to increase beta-tubulin production in cultured neonatal
rat cardiac myocytes. Results indicate that both contractile activity
and load due to passive stretch increase beta-tubulin protein content
in neonatal rat cardiac myocytes through accumulation of beta-tubulin
mRNA, which occurs without increased beta-tubulin gene transcription.
Western blot analysis demonstrated that contraction resulted in the
accumulation of beta-tubulin in neonatal rat cardiac myocytes above
increases observed in the content of total cellular protein. Northern
blot analysis indicated that beta-tubulin mRNA content increased in
response to both stretch and contraction, as well as alpha-adrenergic
stimulation. Alpha-adrenergic agonists which lead to
pathophysiological growth in cardiac myocytes also stimulated an
increase beta-tubulin mRNA content. Treatment of contracting neonatal
cardiac myocytes with AII further increased beta-tubulin mRNA
content, while AII treatment in arrested neonatal cardiac myocytes
failed to increase beta-tubulin mRNA. Nuclear run-on experiments
indicate that contraction stimulates beta-tubulin mRNA accumulation
without an increase in beta-tubulin gene transcription. These results
imply that tubulin production in cultured cardiac myocytes can be
regulated directly by mechanical forces. In mechanically-challanged
hearts, the accumulation of beta-tubulin and the development of
contractile dysfunction may be directly related to the mechanical
forces imposed upon the myocardium during the onset and progression
of cardiovascular disease.
Received 22 November 1995; accepted in final form 21 February
1996.
APS Manuscript Number C702-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96