Renal ischemia induces tropomyosin dissociation-destabilizing microvilli microfilaments

Sharon L. Ashworth, Sarah E. Wean, Silvia Campos-Bilderback, Constance J. Temm-Grove, Erica L. Southgate, Bernadette Vrhovski, Peter Gunning, Ron P. Weinberger, Bruce Molitoris

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Ischemic-induced cell injury results in rapid duration-dependent actin-depolymerizing factor (ADF)/cofilin-mediated disruption of the apical microvilli microfilament cores. Because intestinal microvillar microfilaments are bound and stabilized in the terminal web by the actin-binding protein tropomyosin, we questioned whether a protective effect of tropomyosin localization to the terminal web of the proximal tubule microfilament cores is disrupted during ischemic injury. With tropomyosin-specific antibodies, we examined rat cortical sections under physiological conditions and following ischemic injury by confocal microscopy. In addition, Western blot analysis of cortical extracts and urine was undertaken. Our studies demonstrated the presence of tropomyosin isoforms in the proximal tubule microvillar terminal web under physiological conditions and their dissociation in response to 25 min of ischemic injury. This correlated with the excretion of tropomyosin-containing plasma membrane vesicles in urine from ischemic rats. In addition, we noted increased tropomyosin Triton X-100 solubility following ischemia in cortical extracts. These studies suggest tropomyosin binds to and stabilizes the microvillar microfilament core in the terminal web under physiological conditions. With the onset of ischemic injury, we propose that tropomyosin dissociates from the microfilament core providing access to microfilaments in the terminal web for F-actin binding, severing and depolymerizing actions of ADF/cofilin proteins.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number5 55-5
DOIs
StatePublished - May 2004

Fingerprint

Tropomyosin
Microvilli
Actin Cytoskeleton
Ischemia
Kidney
Destrin
Actin Depolymerizing Factors
Wounds and Injuries
Urine
Microfilament Proteins
Octoxynol
Confocal Microscopy
Solubility
Actins
Protein Isoforms
Western Blotting
Cell Membrane
Antibodies

Keywords

  • Actin-depolymerizing factor
  • Brush border
  • Cofilin

ASJC Scopus subject areas

  • Physiology

Cite this

Renal ischemia induces tropomyosin dissociation-destabilizing microvilli microfilaments. / Ashworth, Sharon L.; Wean, Sarah E.; Campos-Bilderback, Silvia; Temm-Grove, Constance J.; Southgate, Erica L.; Vrhovski, Bernadette; Gunning, Peter; Weinberger, Ron P.; Molitoris, Bruce.

In: American Journal of Physiology - Renal Physiology, Vol. 286, No. 5 55-5, 05.2004.

Research output: Contribution to journalArticle

Ashworth, Sharon L. ; Wean, Sarah E. ; Campos-Bilderback, Silvia ; Temm-Grove, Constance J. ; Southgate, Erica L. ; Vrhovski, Bernadette ; Gunning, Peter ; Weinberger, Ron P. ; Molitoris, Bruce. / Renal ischemia induces tropomyosin dissociation-destabilizing microvilli microfilaments. In: American Journal of Physiology - Renal Physiology. 2004 ; Vol. 286, No. 5 55-5.
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