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AJP - Renal Physiology, Vol 271, Issue 6 1234-F1238, Copyright © 1996 by American Physiological Society
ARTICLES |
Z. Zhang and D. M. Cohen
Division of Nephrology, Hypertension, and Clinical Pharmacology, Oregon Health Sciences University, Portland, USA.
The mitogen-activated protein kinases (MAPKs), p38 and jun kinase (JNK), are activated by diverse stressors in cells of nonrenal medullary origin. Epithelial cells of the renal medulla are among the very few cells of higher eukaryotes routinely subjected to hyperosmotic stress, composed of principally NaCl and urea. Hyperosmotic NaCl activated p38 and JNK in a time- and dose-dependent fashion in cells of the murine terminal inner medullary collecting duct cell line (mIMCD3) as determined by immune complex kinase assay. Hyperosmotic urea exerted a minimal effect upon only p38 activation, which was evident only at 5 min. The NaCl effect was dose dependent to 800 mosmol/kgH2O; 800 mosmol/kgH2O urea, in contrast, exerted no effect. Consistent with these observations, NaCl (800 mosmol/kgH2O) but not urea (800 mosmol/kgH2O) increased tyrosine phosphorylation of p38 and JNK at 10 min. 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 MAPKs. Urea, in contrast, exerted virtually no effect; therefore, cellular protection from urea stress operates through a mechanism distinct from the stress-responsive MAPKs.
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Z. Zhang and D. M. Cohen Urea activates ribosomal S6 kinase (RSK) in a MEK-dependent fashion in renal mIMCD3 cells Am J Physiol Renal Physiol, January 1, 1998; 274(1): F73 - F78. [Abstract] [Full Text] [PDF]
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H. Zhao, W. Tian, and D. M. Cohen Rottlerin inhibits tonicity-dependent expression and action of TonEBP in a PKCdelta -independent fashion Am J Physiol Renal Physiol, April 1, 2002; 282(4): F710 - F717. [Abstract] [Full Text] [PDF]
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