Nh4cl-induced hypertrophy is mediated by weak base effects and is
independent of cell cycle processes.
Franch, Harold A., and Patricia A. Preisig.
Department of Internal Medicine, University of Texas Southwestern
Medical Center, Dallas, Texas 75235-8856
APStracts 2:0353C, 1995.
Renal hypertrophy occurs in a number of clinical conditions, some of
which are associated with increases in ambient ammonia
concentrations. NH4Cl induces hypertrophy in cultured renal
epithelial cells. The present studies examined the mechanism of
NH4Cl-induced hypertrophy in NRK-52E cells. Hypertrophy was also
induced by methylammonium chloride, a related weak base, but not by
tetramethylammonium chloride, a weak base analog that can neither
accept nor donate protons. Bafilomycin A1, an inhibitor of vacuolar H
pumps, also induced hypertrophy. Taken together these studies suggest
that NH4Cl-induced hypertrophy is mediated by its weak base property,
allowing it to enter and alkalinize acid vesicular compartments.
Additional studies demonstrated that NH4Cl-induced hypertrophy is not
mediated by modulation of cell cycle processes. NH4Cl addition had no
effect on: c-fos mRNA abundance, typically associated with entrance
into the cell cycle; cyclin E protein abundance, which increases as
cells progress through G1; or protein synthesis, which also increases
during G1. In addition, inactivation of pRB by overexpression of
HPV16 E7, which inhibits cell cycle-dependent hypertrophy, had no
effect on the ability of NH4Cl to induce hypertrophy. Based on these
data, we postulate that in hypertrophic conditions associated with
increased ammoniagenesis, hypertrophy is mediated by vesicular
alkalinization, and occurs independent of processes that govern
progression through the cell cycle.
Received 24 May 1995; accepted in final form 25 September 1995.
APS Manuscript Number C302-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95