A combination of nacl and urea enhances survival of imcd cells to
hyperosmolality.
Santos, Bento C., Alejandro Chevaile, Marie-Jos[acute]ee
H[acute]ebert, Jane Zagajeski, and Steven R. Gullans.
Renal Division, Department of Medicine, Brigham and Women's
Hospital and Harvard Institutes of Medicine, Boston, MA 02115
APStracts 5:0065F, 1998.
Physiological adaptation to the hyperosmolar milieu of the renal
medulla involves a complex series of signaling and gene expression
events in which NaCl and urea activate different cellular processes.
In the present study we evaluated the effects of NaCl and urea,
individually and in combination, on the viability of murine inner
medullary collecting duct (mIMCD3) cells. Exposure to hyperosmolar
NaCl or urea caused comparable dose- and time-dependent decreases in
cell viability such that 700 mOsm killed greater than 90% of the
cells within 24 hrs. In both cases, cell death was an apoptotic
event. For NaCl, loss of viability at 24 hours paralleled decreases
in RNA and protein synthesis at 4 hours whereas lethal doses of urea
had little or no effect on these biosynthetic processes. Cell cycle
analysis showed both solutes caused a slowing of the G2/M phase.
Surprisingly, cells exposed to a combination of NaCl + urea were
significantly more osmotolerant such that 40% survived 900 mOsm.
Madin-Darby canine kidney (MDCK) cells but not human umbilical vein
endothelial cells (HUVECs) also exhibited a similar osmotolerance
response. Enhanced survival was not associated with a restoration of
normal biosynthetic rates or cell cycle progression. However, the
combination of NaCl + urea resulted in a shift in Hsp70 expression
that appeared to correlate with survival. In conclusion, hyperosmolar
NaCl and urea activate independent and complementary cellular
programs that confer enhanced osmotolerance to renal medullary
epithelial cells.
Received 3 November 1997; accepted in final form 4 March 1998.
APS Manuscript Number F347-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 6 April 1998