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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Young, E. E. Farber, J. L. Schanne, F. A. Kane, A. B. |
| Abstract | The role of Ca2+ in toxic liver cell death was studied with primary cultures of adult rat hepatocytes. Within 1 hr of exposure to phalloidin, a bicyclic heptapeptide isolated from the mushroom Amanita pahlloides, at 50 micrograms/ml, 60--70% of the cells were dead (trypan blue stainable). There was no loss of viability of the same cells exposed to phalloidin in culture medium devoid of Ca2+. A marked structural alteration of the surface of the phalloidin-treated hepatocytes characterized by innumerable evaginations seen by scanning electron microscopy occurred in the presence or absence of Ca2+. Pretreatment of the cells with cytochalasin B at 10 micrograms/ml prevented the surface alteration and the death of the cells in Ca2+ medium. Exposure of the cells to phalloidin in the absence of Ca2+ followed by exposure to cytochalasin B and then to Ca2+ also prevented the cell death. These results suggest a two-step mechanism by which phalloidin causes liver cell death. Initially phalloidin interacts in a Ca2+-independent process with cell membrane-associated actin. The second step is a Ca2+-dependent process that most likely represents an increased influx of Ca2+ across a compromised cell membrane permeability barrier and down the steep concentration gradient that exists between the outside and inside of the cell. These results strengthen the hypothesis that disturbances in Ca2+ homeostasis induced in vivo by a variety of hepatotoxins are causally related to liver cell death. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 77 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1980-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium Pharmacology Cell Survival Drug Effects Liver Oligopeptides Phalloidine Actins Metabolism Animals Calcimycin Cells, Cultured Cytochalasin B Cytoskeleton Drug Synergism Cytology Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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