Expression of protein kinase c isoforms during cardiac ventricular
development.
Clerk, Angela, Marie A. Bogoyevitch, Stephen J. Fuller, Antigone
Lazou, Peter J. Parker, and Peter H. Sugden.
Department of Cardiac Medicine, National Heart and Lung Institute,
University of London, London SW3 6LY, United Kingdom; and Imperial
Cancer Research Fund Laboratories, London WC2A 3PX, United
Kingdom
APStracts 2:0091H, 1995.
The expression of protein kinase C (PKC) isoforms (PKC-[alpha], PKC
-[beta]1, PKC-[delta], PKC- and PKC-_) was studied by immunoblotting
in whole ventricles of rat hearts during post-natal development (1 -
26 days) and in the adult. PKC-[alpha], PKC-[beta]1, PKC-[delta],
PKC- and PKC-_ were detected in ventricles of 1-day-old rats,
although PKC-[alpha] and PKC[beta]1 were only barely detectable. All
isoforms were rapidly down-regulated during development, with
abundances relative to total protein declining in the adult to <25%
of 1-day-old values. PKC-[beta]1 was not detectable in adult
ventricles. The specific activity of PKC was also down-regulated. The
rat ventricular myocyte becomes amitotic soon after birth but
continues to grow, increasing its protein content 40- to 50-fold
between the neonate and the 300 g adult. An important question is
thus whether the amount of PKC per myocyte is down-regulated. Using
isolated cells, immunoblotting showed that the contents per myocyte
of PKC-[alpha] and PKC- increased about 10-fold between the neonatal
and adult stages. In rat ventricles, the rank of association with the
particulate fraction was PKC-[delta]>PKC- >PKC-_. Association of
these isoforms with the particulate fraction was less in the adult
than in the neonate. In primary cultures of ventricular myocytes
prepared from neonatal rat hearts, 1 [mu]M 12-O-tetradecanoylphorbol
13-acetate (TPA) elicited translocation of PKC-[alpha], PKC-[delta]
and PKC- from the soluble to the particulate fraction in <1 min,
after which time no further translocation was observed. Prolonged
exposure (16 h) of myocytes to 1 [mu]M TPA caused essentially
complete down-regulation of these isoforms, although down-regulation
of PKC- was slower than for PKC-[delta]. In contrast, PKC-_ was
neither translocated nor down-regulated by 1 [mu]M TPA.
Immunoblotting of human ventricular samples also revealed down
-regulation of PKC relative to total protein during fetal/postnatal
development.
Received 16 May 1994; accepted in final form 1 March 1995.
APS Manuscript Number H415-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.