Date of Award
2001
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biology
Abstract
Ischemic or anoxic ATP depletion is the primary cause of acute renal failure (ARF) and is estimated to occur in 5% of all hospitalized patients. ATP depletion results in the rapid disruption of the actin cytoskeleton in renal proximal tubule (PT) cells. The disruption of the actin cytoskeleton initiates a cascade of structural and functional alterations in anoxic PT, including microvilli retraction, loss of membrane polarity, membrane bleb formation, and the detachment of PT cells into the urinary lumen. These alterations progress in a duration-dependent manner and are reversible during the recovery phase. Understanding of the cellular mechanisms that mediate the injuries observed during anoxia would provide a basis for delaying PT injury or enhancing recovery during the reversible phase. One of the earliest and most dramatic events observed in anoxic PT cells is the loss of microvilli structure at the apical membrane. Actin filaments (F-actin), comprising the core of microvilli structure, dissociate from binding proteins that laterally link the filaments to the plasma membrane. Microvillar collapse follows the loss of F-actin structure at the apical membrane, but the mechanisms of F-actin disruption are not well understood. The research program presented here employed morphological and biochemical techniques to characterize the disruption of F-actin in anoxic PT cells. The results demonstrate that during ATP-depletion, F-actin is sequestered in the perinuclear region of PT cells. Actin sequestration coincided with microvilli disruption and progressed in a duration-dependent manner. Using specific actin-disrupting chemicals, we propose that the severance of actin filaments is the mechanism responsible for disruption of the actin cytoskeleton. The pathologies characterized in this report were observed in both freshly isolated tissue preparations and the cultured PT cell line LLC-PKI. The significance of these pathologies in acute renal cell injury is discussed.
Recommended Citation
White, Peter A., "Microvillar Disruption And F -Actin Sequestration In Anoxic Proximal Tubular Cells" (2001). All-Inclusive List of Electronic Theses and Dissertations. 1023.
https://scholars.indianastate.edu/etds/1023