| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Renal Epithelial Biology Experimental Laboratories, Indiana University Department of Medicine, and Roudebush Veterans Administration Medical Center, Indianapolis, Indiana 46202-5116; and 2 Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870
Breakdown of proximal tubule cell apical membrane microvilli is an early-occurring hallmark of ischemic acute renal failure. Intracellular mechanisms responsible for these apical membrane changes remain unknown, but it is known that actin cytoskeleton alterations play a critical role in this cellular process. Our laboratory previously demonstrated that ischemia-induced cell injury resulted in dephosphorylation and activation of the actin-binding protein, actin depolymerizing factor [(ADF); Schwartz, N, Hosford M, Sandoval RM, Wagner MC, Atkinson SJ, Bamburg J, and Molitoris BA. Am J Physiol Renal Fluid Electrolyte Physiol 276: F544-F551, 1999]. Therefore, we postulated that ischemia-induced ADF relocalization from the cytoplasm to the apical microvillar microfilament core was an early event occurring before F-actin alterations. To directly investigate this hypothesis, we examined the intracellular localization of ADF in ischemic rat cortical tissues by immunofluorescence and quantified the concentration of ADF in brush-border membrane vesicles prepared from ischemic rat kidneys by using Western blot techniques. Within 5 min of the induction of ischemia, ADF relocalized to the apical membrane region. The length of ischemia correlated with the time-related increase in ADF in isolated brush-border membrane vesicles. Finally, depolymerization of microvillar F-actin to G-actin was documented by using colocalization studies for G- and F-actin. Collectively, these data indicate that ischemia induces ADF activation and relocalization to the apical domain before microvillar destruction. These data further suggest that ADF plays a critical role in microvillar microfilament destruction and apical membrane damage during ischemia.
actin depolymerizing factor; cofilin; acute renal failure; actin cytoskeleton
This article has been cited by other articles:
|
|
 |
|
  B. A. Molitoris, P. C. Dagher, R. M. Sandoval, S. B. Campos, H. Ashush, E. Fridman, A. Brafman, A. Faerman, S. J. Atkinson, J. D. Thompson, et al. siRNA Targeted to p53 Attenuates Ischemic and Cisplatin-Induced Acute Kidney Injury J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1754 - 1764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Campos, S. L. Ashworth, S. Wean, M. Hosford, R. M. Sandoval, M. A. Hallett, S. J. Atkinson, and B. A. Molitoris Cytokine-induced F-actin reorganization in endothelial cells involves RhoA activation Am J Physiol Renal Physiol, March 1, 2009; 296(3): F487 - F495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Devarajan Update on Mechanisms of Ischemic Acute Kidney Injury J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1503 - 1520. [Full Text] [PDF]
|
|
|
|
|
|
M. V. Suurna, S. L. Ashworth, M. Hosford, R. M. Sandoval, S. E. Wean, B. M. Shah, J. R. Bamburg, and B. A. Molitoris Cofilin mediates ATP depletion-induced endothelial cell actin alterations Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1398 - F1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Tanner, R. M. Sandoval, B. A. Molitoris, J. R. Bamburg, and S. L. Ashworth Micropuncture gene delivery and intravital two-photon visualization of protein expression in rat kidney Am J Physiol Renal Physiol, September 1, 2005; 289(3): F638 - F643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. M. Welham, P. R. Riley, A. Wade, M. Hubank, and A. S. Woolf Maternal diet programs embryonic kidney gene expression Physiol Genomics, June 16, 2005; 22(1): 48 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Ivanov, I. C. McCall, C. A. Parkos, and A. Nusrat Role for Actin Filament Turnover and a Myosin II Motor in Cytoskeleton-driven Disassembly of the Epithelial Apical Junctional Complex Mol. Biol. Cell, June 1, 2004; 15(6): 2639 - 2651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Ashworth, S. E. Wean, S. B. Campos, C. J. Temm-Grove, E. L. Southgate, B. Vrhovski, P. Gunning, R. P. Weinberger, and B. A. Molitoris Renal ischemia induces tropomyosin dissociation-destabilizing microvilli microfilaments Am J Physiol Renal Physiol, May 1, 2004; 286(5): F988 - F996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Bonventre and J. M. Weinberg Recent Advances in the Pathophysiology of Ischemic Acute Renal Failure J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2199 - 2210. [Full Text] [PDF]
|
|
|
|
|
|
J. V. Bonventre Dedifferentiation and Proliferation of Surviving Epithelial Cells in Acute Renal Failure J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S55 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Ashworth, E. L. Southgate, R. M. Sandoval, P. J. Meberg, J. R. Bamburg, and B. A. Molitoris ADF/cofilin mediates actin cytoskeletal alterations in LLC-PK cells during ATP depletion Am J Physiol Renal Physiol, April 1, 2003; 284(4): F852 - F862. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
