Cisplatin effects on F-actin and matrix proteins precede renal tubular cell detachment and apoptosis in vitro.

In primary cultures of porcine proximal tubular kidney cells and LLC-PK1 cells cisplatin (5 - 50 microM) 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.