Chronic tpa treatment inhibits expression of proximal tubule
-specific properties by llc-pk1 cells.
Amsler, Kurt, Judith Murray, Racquel Cruz, and Jen-Li Chen.
Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson
Medical School, Piscataway, NJ 08854
APStracts 2:0338C, 1995.
Confluent LLC-PK1 cell populations expressed progressively proximal
tubule-specific properties, including gamma-glutamyl transpeptidase
activity, Na-hexose symport activity, alkaline phosphatase activity,
and villin protein. This was parallelled by an increase in villin
protein manifested at the single cell level. Chronic treatment with
12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited expression of
proximal tubule-specific properties at the levels of enzyme activity,
protein content, and mRNA content. Inhibition occurred in all cells
of the population. TPA treatment induced a decrease in total protein
kinase C (PKC)-alpha protein content and a change in subcellular
localization from predominantly soluble to predominantly particulate.
PKC-epsilon protein content was unchanged by TPA treatment. PKC
-epsilon was localized in both soluble and particulate fractions of
control cells but was localized predominantly in particulate fraction
following TPA treatment. PKC-delta was barely detectable in control
cells but content was markedly increased by TPA. These results
suggest that TPA-induced inhibition of expression of proximal tubule
-specific properties is mediated through modulation of content and/or
subcellular localization of one or more PKC isozymes, likely PKC
-alpha.
Received 12 June 1995; accepted in final form 18 July 1995.
APS Manuscript Number C327-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.