Antimycin A-Induced Defenestration in Rat Hepatic... : Hepatology (original) (raw)
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Antimycin A-Induced Defenestration in Rat Hepatic Sinusoidal Endothelial Cells
Braet, Filip1; Muller, Michael2; Vekemans, Katrien1; Wisse, Eddie1; Le Couteur, David G.*,2
1_Laboratory for Cell Biology and Histology, Free University of Brussels, Laarbeeklaan, Brussels–Jette, Belgium_
2_Centre for Education and Research on Ageing, and ANZAC Research Institute, University of Sydney, Concord RG Hospital, Sydney, NSW, Australia_
* Centre for Education and Research on Ageing, University of Sydney, Concord RG Hospital, NSW 2139 Australia. fax: (612) 9767–5419; E-mail: [email protected].
Received: 4 March 2003; Accepted: 17 May 2003
Abstract
Liver sinusoidal endothelial cells (LSECs) possess fenestrae arranged in sieve plates. Hepatic endothelial fenestrae are open pores approximately 100 to 200 nm in diameter. Alterations in their number or diameter by hormones, xenobiotics, and diseases have important implications for hepatic microcirculation and function. Numerous reports of hepatotoxin–induced defenestration suggest that the cytoskeleton and the energy status of hepatic endothelial cells play a key role in the regulation of fenestrae. Therefore, we investigated the effect of antimycin A, an inhibitor of mitochondrial energy production, on the number of fenestrae in cultured LSECs using high–resolution microscopy and immunocytochemistry. Prolonged incubation (greater than 30 min) with antimycin A resulted in defenestrated cells and coincided with the appearance of F–actin dots, whereas the distribution of G–actin remained unchanged. Adenosine triphosphate (ATP) was depleted dramatically to less than 5% within 30 minutes within the LSECs. After treatment with antimycin A, unusual elevated fenestrated complexes were apparent, organized as a meshwork of anastomosing fenestrae at the center of and above the sieve plates. The position and appearance of these novel structures and their association with defenestration suggest that they are implicated in the process of defenestration. In conclusion, the results of experiments with antimycin A suggest that ATP is needed to maintain fenestrae and the underlying fenestrae–associated cytoskeleton rings that maintain fenestrae patency. Antimycin A–induced defenestration of LSECs is associated with the development of a structure in the sieve plate that appears to be intrinsically involved in defenestration.
Copyright © 2003 American Association for the Study of Liver Diseases.