Differential effects of egf on the repair of cellular functions
following dichlorovinyl-l-cysteine-induced injury.
Nowak, Grazyna, Kenneth B. Keasler, Douglas E. McKeller, and Rick G.
Schnellmann.
University of Arkansas for Medical Sciences, Department of
Pharmacology and Toxicology, 4301 West Markham St., Little Rock, AR
72205-7199
APStracts 5:0183F, 1998.
This study examined the repair of renal proximal tubule cellular
(RPTC) functions following sublethal injury induced by the
nephrotoxicant S-(1,2-dichlorovinyl)-L-cysteine (DCVC). DCVC exposure
resulted in 31% cell death and loss 24 h following the treatment.
Monolayer confluence recovered through migration/spreading but not
proliferation after 6 days. Basal, uncoupled, and ouabain-sensitive
oxygen consumption (QO2) decreased 47, 76, and 62%, respectively, 24
h after DCVC exposure. Na+-K+-ATPase activity and Na+-dependent
glucose uptake were inhibited 80 and 68%, respectively, 24 h after
DCVC exposure. None of these functions recovered over time. Addition
of epidermal growth factor (EGF) following DCVC exposure did not
prevent decreases in basal, uncoupled and ouabain-sensitive QO2s and
Na+-K+-ATPase activity but promoted their recovery over 4-6 days. In
contrast, no recovery of Na+-dependent glucose uptake occured in the
presence of EGF. These data show that: 1) DCVC exposure decreases
mitochondrial function, Na+-K+-ATPase activity, active Na+ transport
and Na+-dependent glucose uptake in sublethally-injured RPTC; 2)
DCVC-treated RPTC do not proliferate nor regain their physiological
functions in this model; and 3) EGF promotes recovery of
mitochondrial function and active Na+ transport but not Na+-dependent
glucose uptake. These results suggest that cysteine conjugates may
cause renal dysfunction, in part, by decreasing RPTC functions and
inhibiting their repair.
Received 6 July 1998; accepted in final form 8 October 1998.
APS Manuscript Number F161-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998