New insights into the cell biology of ischemic acute renal failure.
Proximal tubule cells play an essential role in the reabsorption of ions, water, and solutes from the glomerular filtrate. This is accomplished, in large part, by having a surface membrane polarized into structurally, biochemically, and physiologically distinct apical and basolateral membrane domains separated by cellular junctional complexes. Establishment and maintenance of these unique membrane domains are essential for the normal functioning of the cell. Ischemia results in the duration-dependent loss of apical and basolateral surface membrane lipid and protein polarity. Loss of surface membrane polarity is preceded by disruption of the microfilament network and opening of cellular tight junctions. Surface membrane lipids and proteins are then free to diffuse laterally within the bilayer into the alternate membrane domain. Functionally, ischemia-induced loss of epithelial polarity has been shown to be responsible for reduced sodium and glucose reabsorption. Reduced Na+ reabsorption has been related to redistribution of Na+, K(+)-ATPase into the apical membrane. During recovery from ischemic injury, proximal tubule cells undergo remodeling of the surface membrane such that the unique apical and basolateral membrane domains are reestablished, allowing for the return of normal cellular function.
Molitoris
B A
BA
Department of Medicine, University of Colorado, School of Medicine, Denver.
D000199:Actins / Q000378:metabolism; D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000503:physiopathology; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism
D000199:Actins; D008563:Membrane Lipids; D008565:Membrane Proteins