| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea, Republic of; Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Korea, Republic of
2 Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea, Republic of; Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Korea, Republic of; Nephrology and Dialysis Unit, YanBian University Medical College, Yanji, China
3 Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Korea, Republic of; Department of Anatomy, The Catholic University of Korea, Seoul, Korea, Republic of
4 Research Institute of Medical Science, Chonnam National University, Gwangju, Korea, Republic of
5 Laboratory of Ocular Therapeutics, National Institutes of Health, Bethesda, MD, USA
6 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
7 Renal Division, Department of Medicine and Physiology, Emory University School of Medicine, Atlanta, GA, USA
* To whom correspondence should be addressed. E-mail: yangch{at}catholic.ac.kr.
The aim of this study was to evaluate the long-term effects of cyclosporine (CsA) treatment on urinary concentration ability. Rats were treated daily for four weeks with vehicle (VH, olive oil, 1 ml/kg s.c.) or CsA (15 mg/kg s.c.). The influence of CsA on the kidney's ability to
concentrate urine was evaluated using functional parameters and expression of aquaporins (AQP-1-4) and of urea transporters (UT-A-1-3, and UT-B). Plasma vasopressin levels and the associated signal pathway were evaluated, and the effect of vasopressin infusion on urine
concentration was observed in VH- and CsA-treated rats. Toxic effects of CsA on tubular cells in the medulla as well as the cortex were evaluated with aldose reductase (AR), Na-K-ATPase-
1 expression and by determining the number of TUNEL-positive cells. Long-term CsA
treatment increased urine volume and fractional excretion of sodium, and decreased urine osmolality and free-water reabsorption compared with VH-treated rats. These functional
changes were accompanied by decreases in the expression of AQP (1-4) and UT (UT-A2, A3, and UT-B), although there was no change of AQP-2 in the cortex and outer medulla and UT-A1
in the inner medulla. Plasma vasopressin levels were not significantly different between two groups, but infusion of vasopressin restored CsA-induced impairment of urine concentration. cAMP levels and Gs protein expression was significantly reduced in CsA-treated rat kidneys compared with VH-treated rat kidneys. CsA treatment decreased the expression of AR and Na- K-ATPase-1 and increased the number of TUNEL-positive renal tubular cells in both the cortex and medulla. Moreover, the number of TUNEL-positive cells correlated with AQP-2 (r = - 0.671, P < 0.05) or UT-A3 (r = - 0.827, P < 0.05) expression within the inner medulla. In conclusion, CsA treatment impairs urine concentrating ability by decreasing AQP and UT expression. Apoptotic cell death within the inner medulla, at least partially accounts for the
CsA-induced urinary concentration defect.
This article has been cited by other articles:
|
|
 |
|
  B. Edemir, S. Reuter, R. Borgulya, R. Schroter, U. Neugebauer, G. Gabriels, and E. Schlatter Acute Rejection Modulates Gene Expression in the Collecting Duct J. Am. Soc. Nephrol., March 1, 2008; 19(3): 538 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Z. Li, B. W. McDill, P. A. Kovach, L. Ding, W. Y. Go, S. N. Ho, and F. Chen Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1606 - C1616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Hasler Interplay between TonEBP and calcineurin-NFATc signaling pathways: a means of optimizing water reabsorption? Focus on "Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress" Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1581 - C1582. [Full Text] [PDF]
|
|
|
|
|
|
S. W. Lim, K. O. Ahn, M. R. Sheen, U. S. Jeon, J. Kim, C. W. Yang, and H. M. Kwon Downregulation of Renal Sodium Transporters and Tonicity-Responsive Enhancer Binding Protein by Long-Term Treatment with Cyclosporin A J. Am. Soc. Nephrol., February 1, 2007; 18(2): 421 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Yang, W. Y. Tam, S. Tam, H. Guo, X. Wu, G. Li, J. F. L. Chau, J. D. Klein, S. K. Chung, J. M. Sands, et al. Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism Am J Physiol Renal Physiol, July 1, 2006; 291(1): F186 - F195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Gooch, R. L. Guler, J. L. Barnes, and J. J. Toro Loss of calcineurin A{alpha} results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus J. Cell Sci., June 15, 2006; 119(12): 2468 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Lim, K.-H. Han, J.-Y. Jung, W.-Y. Kim, C.-W. Yang, J. M. Sands, M. A. Knepper, K. M. Madsen, and J. Kim Ultrastructural localization of UT-A and UT-B in rat kidneys with different hydration status Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2006; 290(2): R479 - R492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Uchida, E. Sohara, T. Rai, M. Ikawa, M. Okabe, and S. Sasaki Impaired Urea Accumulation in the Inner Medulla of Mice Lacking the Urea Transporter UT-A2 Mol. Cell. Biol., August 15, 2005; 25(16): 7357 - 7363. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
