Abstract
Background: Membrane protein kinase C (PKC) activity is increased in frontal cortex
of subjects with bipolar affective disorder, and lithium was demonstrated to inhibit
PKC translocation to membranes. Protein kinase C is anchored to the membrane via the
receptor for activated C kinase-1 (RACK1), suggesting that interactions between these
proteins may be altered in bipolar disease.
Methods: The levels of RACK1 coimmunoprecipitating with PKC isozymes were compared
in homogenates of frontal cortex slices from postmortem bipolar subjects and matched
control subjects.
Results: Receptor for activated C kinase-1 was located exclusively in membranes and,
in control brains, the levels of RACK1 that coimmunoprecipitated with most PKC isozymes
were increased by stimulation with the PKC activator, phorbol 12-myristate, 13-acetate
(PMA). The association of RACK1 with membrane γPKC and ζPKC was increased under basal
conditions in bipolar relative to control brains. Stimulation with PMA increased the
amount of RACK1 that coimmunoprecipitated with the α, β, γ, δ, and εPKC isozymes,
but not ζPKC, in bipolar tissues over that elicited in control tissues.
Conclusions: These data suggest that the increased association of RACK1 with PKC isozymes
may be responsible for the increases in membrane PKC and in its activation that were
previously observed in frontal cortex of bipolar affective disorder brains.
Keywords
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Article info
Publication history
Accepted:
March 12,
2001
Received in revised form:
March 2,
2001
Received:
November 8,
2000
Identification
Copyright
© 2001 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
