Lysophosphatidic acid-induced calcium mobilisation and
proliferation in kidney proximal tubular cells.
Dixon, Richard J., Ken Young and Nigel J. Brunskill,.
1Department of Cell Physiology and Pharmacology, Leicester
University School of Medicine, Leicester, U.K., 2Department of
Nephrology, Leicester General Hospital, Leicester, U.K.
APStracts 5:0173F, 1998.
Patients with proteinuria tend to develop progressive renal disease
with proximal tubular cell atrophy and interstitial scarring. It has
been suggested that the nephrotoxicity of albuminuric states is may
be due to the protein molecule itself or by lipids, such as
lysophosphatidic acid (LPA), that albumin carries. LPA was found to
cause a transient increase in [Ca2+]I in opossum kidney proximal
tubule cells (OK) that was maximal at 100 (M LPA and was dose
dependent with an EC50 of 2.6 x 10-6 M . This Ca2+ mobilisation was
from both internal stores and across the plasma membrane and was
pertussis toxin (PTX) insensitive. Treatment of OK cells with 100 (M
LPA for 5 minutes was found to cause a two-fold increase in [3H]
thymidine incorporation and a three to five-fold increase over
control after 24 hours. This was highly PTX - sensitive and
insensitive to pre-treatment with the tyrosine kinase inhibitors
Genestein and Herbimycin A. These findings may be of significance in
the progression of renal disease and indicate the potential
importance of lipids in modulating proximal tubule cell function and
growth.
Received 1 June 1998; accepted in final form 25 September 1998.
APS Manuscript Number F135-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 20 October 1998