Abstract
In primary cultures of porcine proximal tubular kidney cells and LLC-PK1 cells cisplatin (5–50 μM) caused apoptosis and cell detachment; in both systems cell detachment occurred, preceded by a loss of cytoskeletal F-actin stress fibers within 4–6 h, and a reduction of mRNA encoding for fibronectin, collagen a2 type (IV) and laminin B2 within 17–41 h. Prevention of F-actin damage by phalloidin prevented nuclear fragmentation, suggesting a relation between F-actin damage and apoptosis. Overexpression of Bcl-2 also prevented apoptosis, but did not prevent damage to the F-actin skeleton or the reduction of mRNA expression of the matrix proteins. These results suggest that Bcl-2 overexpression interferes with apoptotic signals downstream of F-actin. The relevance of these results for cell detachment in kidney toxicity is discussed.
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Kruidering, M., van de Water, B., Zhan, Y. et al. Cisplatin effects on F-actin and matrix proteins precede renal tubular cell detachment and apoptosis in vitro. Cell Death Differ 5, 601–614 (1998). https://doi.org/10.1038/sj.cdd.4400392
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DOI: https://doi.org/10.1038/sj.cdd.4400392
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