Prior heat stress enhances survival of renal epithelial cells after
atp depletion.
Wang, Y-H., and S. C. Borkan.
Thorndike Memorial Laboratory, Room #416, Boston University Medical
Center, Boston City Hospital, 818 Harrison Avenue, Boston, MA
02118
APStracts 3:0037F, 1996.
HSP 72 kDa (HSP 72) is an inducible cytoprotectant protein. Although
transient renal ischemia in vivo induces HSP 72, it is not known
whether prior heat stress protects renal epithelial cells from injury
mediated by ATP depletion. To evaluate this hypothesis, opossum
kidney (OK) cells were exposed to sodium cyanide and 2-deoxy-D
-glucose in the absence of medium glucose, a maneuver that reduced
cell ATP content to < 10% of the control value within 10 mins
and decreased cell survival. One day after 2 hrs of ATP depletion, OK
cells previously exposed to heat stress (to induce accumulation of
HSP 72) exhibited marked improvement in survival (a > 4-fold
increase in total DNA, less uptake of vital dye and less release of
LDH) than cells subjected to ATP depletion alone (23.0 + 1.6 vs. 34.1
+ 1.2 % of total LDH, respectively). Enhanced clonogenicity post-heat
stress was completely prevented by cycloheximide and positively
correlated with the steady state content of HSP 72. In the recovery
period after ATP depletion, cell ATP content, maximum mitochondrial
ATP production rate and total LDH activity were all significantly
higher in cells with abundant HSP 72. Although the protective effects
associated with heat stress are likely to be multifactoral, preserved
cell metabolism and higher ATP content could enhance cellular repair
processes after ATP depletion.
Received 14 February 1995; accepted in final form 6 November
1995.
APS Manuscript Number F54-5.
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