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 mu M) 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 aa 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.