Abstract
The beta-adrenergic receptor system of the failing human heart is
markedly desensitized. We have recently postulated that this desensitization
may in part be caused by an increase in beta-adrenergic receptor
kinase (beta ARK) expression. beta ARK is thought to effect desensitization
by acting in concert with an inhibitor protein, called beta-arrestin.
Two isoforms have been identified both for beta ARK and for beta-arrestin.
In the present study, we have investigated the expression of the
individual isoforms of beta-arrestin and of beta ARK in left ventricles
from failing and control human hearts. mRNAs for all four proteins,
beta-arrestin-1, beta-arrestin-2, beta ARK-1, and beta ARK-2, were
identified in human heart. Quantitation by reverse-transcription
polymerase chain reactions showed that in heart failure there were
no changes of the mRNA levels for beta-arrestin-1 and beta-arrestin-2,
a slight (< 50%) increase of the mRNA for beta ARK-2, and a threefold
increase for beta ARK-1 mRNA. At the protein level, beta-arrestin-1
was readily detected by Western blotting in human heart. Its absolute
values were approximately 350 fmol/mg cytosolic protein, and its
expression was not changed in heart failure. beta-Arrestin-2 levels
were too low to be detectable using the same methods. beta ARK levels
as determined by enzymatic activity were approximately 20 fmol/mg
cytosolic protein (beta ARK-1 plus beta ARK-2) and thus almost 20-fold
lower than those of beta-arrestin. beta ARK levels were increased
approximately twofold in heart failure.(ABSTRACT TRUNCATED AT 250
WORDS)
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