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-P K1 cells cisplatin (5-50 mu M) caused apoptosis and cell detachment; i n both systems cell detachment occurred, preceded by a loss of cytoske letal F-actin stress fibers within 4-6 h, and a reduction of mRNA enco ding for fibronectin, collagen aa type (IV) and laminin B2 within 17-4 1 h, Prevention of F-actin damage by phalloidin prevented nuclear frag mentation, 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.