HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Dmitrieva, N. I. Articles by Ferraris, J. D. Search for Related Content PubMed PubMed Citation Articles by Dmitrieva, N. I. Articles by Ferraris, J. D.

INVITED REVIEW

DNA damage and osmotic regulation in the kidney

Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Department of Health and Human Services, Bethesda, Maryland

Renal medullary cells normally are exposed to extraordinarily high interstitial NaCl concentration as part of the urinary concentrating mechanism, yet they survive and function. Acute elevation of NaCl to a moderate level causes transient cell cycle arrest in culture. Higher levels of NaCl, within the range found in the inner medulla, cause apoptosis. Recently, it was surprising to discover that even moderately high levels of NaCl cause DNA double-strand breaks. The DNA breaks persist in cultured cells that are proliferating rapidly after adaptation to high NaCl, and DNA breaks normally are present in the renal inner medulla in vivo. High NaCl inhibits repair of broken DNA both in culture and in vivo, but the DNA is rapidly repaired if the level of NaCl is reduced. The inhibition of DNA repair is associated with suppressed activity of some DNA damage-response proteins like Mre11, Chk1, and H2AX but not that of others, like GADD45, p53, ataxia telangiectasia-mutated kinase (ATM), and Ku86. In this review, we consider possible mechanisms by which the renal cells escape the known dangerous consequences of persistent DNA damage. Furthermore, we consider that the persistent DNA damage may be a sensor of hypertonicity that activates ATM kinase to provide a signal that contributes to protective osmotic regulation.

hypertonicity; renal medulla; apoptosis; cell cycle delay

This article has been cited by other articles:

				T. S. Gunasekera, L. N. Csonka, and O. Paliy Genome-Wide Transcriptional Responses of Escherichia coli K-12 to Continuous Osmotic and Heat Stresses J. Bacteriol., May 15, 2008; 190(10): 3712 - 3720. [Abstract] [Full Text] [PDF]

				J. Wang, N. Pabla, C.-Y. Wang, W. Wang, P. V. Schoenlein, and Z. Dong Caspase-mediated cleavage of ATM during cisplatin-induced tubular cell apoptosis: inactivation of its kinase activity toward p53 Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1300 - F1307. [Abstract] [Full Text] [PDF]

				S. A. Kempson, J. M. Edwards, and M. Sturek Inhibition of the renal betaine transporter by calcium ions Am J Physiol Renal Physiol, August 1, 2006; 291(2): F305 - F313. [Abstract] [Full Text] [PDF]