G. Nikcevic et al., Mechanical activity in heart regulates translation of alpha-myosin heavy chain mRNA but not its localization, AM J P-HEAR, 45(6), 1999, pp. H2013-H2019
Citations number
30
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Mechanical inactivity depresses protein expression in cardiac muscle tissue
and results in atrophy. We explore the mechanical transduction mechanism i
n spontaneously beating neonatal rat cardiomyocytes expressing the alpha-my
osin heavy chain (alpha-MyHC) isoform by interfering with cross-bridge func
tion [2,3-butanedione monoxime (BDM), 7.5 mM] without affecting cell calciu
m. The polysome content and alpha-MyHC mRNA levels in fractions from a; suc
rose gradient were analyzed. BDM treatment blocked translation at initiatio
n (162 +/- 12% in the nonpolysomal RNA fraction and 43 +/- 6% in the polyso
mal fraction, relative to control as 100%; P < 0.05). There was an increase
in alpha-MyHC mRNA from the nonpolysomal fraction (120.5 +/- 7.7%; P < 0.0
5 compared with control) with no significant change in the heavy polysomes.
In situ hybridization of alpha-MyHC mRNA was used to estimate message abun
dance as a function of the distance from the nucleus. The mRNA was disperse
d through the cytoplasm in spontaneously beating cells as well as in BDM-tr
eated cells (no significant difference). We conclude that direct inhibition
of contractile machinery, but not calcium, regulates initiation of alpha-M
yHC mRNA translation. However, calcium, not pure mechanical signals, appear
s to be important for message localization.