Nacl but not urea activates p38 and jun kinase (jnk) in murine
inner medullary (mimcd3) cells.
Zhang, Zheng, and David M. Cohen.
Division of Nephrology, Hypertension, and Clinical Pharmacology,
Oregon Health Sciences University and Portland Veterans Affairs
Medical Center, Portland, OR 97201
APStracts 3:0166F, 1996.
The mitogen-activated protein kinases, p38 and JNK, are activated by
diverse stressors in cells of non-renal medullary origin. Epithelial
cells of the renal medulla are among the very few cells of higher
eukaryotes routinely subjected to hyperosmotic stress, comprised
principally of NaCl and urea. Hyperosmotic NaCl activated p38 and JNK
in a time- and dose-dependent fashion in mIMCD3 cells, as determined
by immune complex kinase assay. Hyperosmotic urea exerted a minimal
effect upon only p38 activation, which was evident only at 5 minutes.
The NaCl effect was dose-dependent to 800 mOsm; 800 mOsm urea, in
contrast, exerted no effect. Consistent with these observations, NaCl
(800 mOsm) but not urea (800 mOsm) increased tyrosine phosphorylation
of p38 and JNK at 10 minutes. Therefore, even in the extremely
osmotolerant renal medullary mIMCD3 cell line, derived from a tissue
adapted for routine exposure to elevated osmolality, hypertonic NaCl
activated two stress-responsive MAP kinases. Urea, in contrast,
exerted virtually no effect; therefore, cellular protection from urea
stress operates through a mechanism distinct from the stress
-responsive MAPKs.
Received 18 June 1996; accepted in final form 5 September 1996.
APS Manuscript Number F174-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996