Pdgf and il-1 induce and activate specific protein kinase c
isoforms in mesangial cells.
Ganz, Michael B., Brett Saksa, Ramesh Saxena, Karen Hawkins, and John
R. Sedor.
Department of Medicine, Case Western Reserve University and
Divisions of Nephrology, Cleveland VA Medical Center and The
RamelKamp Center for Research, MetroHealth Medical Center, Cleveland,
Ohio
APStracts 3:0038F, 1996.
In vitro and in vivo data suggest a remarkable plasticity in the
differentiated phenotype of intrinsic glomerular cells, which after
injury express new structures and functions. We have shown that a
protein kinase C (PKC) isoform, II, is expressed in diseased, but not
normal glomeruli. Since intrarenal cytokine synthesis has been
implicated in the pathogenesis of progressive glomerular injury, we
have hypothesized that these mediators induce a change in isoform
profile. To test this hypothesis in vitro, we have determined if
platelet-derived growth factor (PDGF) and interleukin-1 (IL-1) alter
the expression or activation of PKC isoforms in cultured mesangial
cells (MCs). By immunoblot and RNase protection assays, both PDGF and
IL-1 induce as early as 2 h de novo synthesis of PKC II. Since MCs
constitutively express PKC a, I, and z, we also determined whether
IL-1 or PDGF alter the activity of these isoforms. PDGF maximally
induced translocation of PKC a (10 min), I (90 min), e (120 min),
and z (120 min) from the cytosolic to the membrane fraction. IL-1, in
contrast, did not alter the distribution of [alpha], I, or at any
time measured but did induce PKC z translocation. These data suggest
inflammatory mediators regulate PKC isoform activity in diseased
glomeruli both by de novo synthesis of unexpressed, and by activation
of constitutively expressed PKC isoforms.
Received 26 September 1995; accepted in final form 25 January
1996.
APS Manuscript Number F324-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96