Pa. Watson et al., CONTRACTILE ACTIVITY AND PASSIVE STRETCH REGULATE TUBULIN MESSENGER-RNA AND PROTEIN-CONTENT IN CARDIAC MYOCYTES, American journal of physiology. Cell physiology, 40(2), 1996, pp. 684-689
Accumulation of tubulin protein and an increased array of microtubules
have been associated with contractile dysfunction in cardiac myocytes
after 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 m
yocytes. Results indicate that both contractile activity and load due
to passive stretch increase beta-tubulin protein content in neonatal r
at cardiac myocytes through accumulation of beta-tubulin mRNA, which o
ccurs 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 observe
d in the content of total cellular protein. Northern blot analysis ind
icated that beta-tubulin mRNA content increased in response to both st
retch and contraction. alpha-Adrenergic agonists that lead to pathophy
siological growth in cardiac myocytes also stimulated an increase in b
eta-tubulin mRNA content. Treatment of contracting neonatal cardiac my
ocytes with angiotensin II (ANG II) further increased beta-tubulin mRN
A content, whereas ANG II treatment in arrested neonatal cardiac myocy
tes failed to increase beta-tubulin mRNA. Nuclear run-on experiments i
ndicate that contraction stimulates beta-tubulin mRNA accumulation wit
hout an increase in beta-tubulin gene transcription. These results imp
ly that tubulin production in cultured cardiac myocytes can be regulat
ed directly by mechanical forces. In mechanically challenged hearts, t
he accumulation of beta-tubulin and the development of contractile dys
function may be directly related to the mechanical forces imposed on t
he myocardium during the onset and progression of cardiovascular disea
se.