F-actin as a functional target for retro-retinoids: a potential role in anhydroretinol-triggered cell death

The retro-retinoids, metabolites of vitamin A (retinol), belong to a family of lipophilic signalling molecules implicated in regulation of cell growth and survival. Growth-promoting properties have been ascribed to 14-hydroxy -retro-retinol (14HRR), while anhydroretinol (AR) was discovered to act as a natural antagonist triggering growth arrest and death by apoptosis, Based on morphological studies and inhibition of apoptosis by the kinase blocker , herbimycin A, it has been suggested that retro-retinoids exhibit their fu nction in the cytosolic compartment. F-actin emerged as a functional target for retro-retinoid action. By FAGS analysis and fluorescence microscopy of phalloidin-FITC labeled cells we demonstrated that F-actin reorganization was an early event in AR-triggered apoptosis, Fluorescence images of AR-tre ated fibroblasts displayed short, thick, stick-like and punctate structures , and membrane ruffles at the cell periphery along with an increased diffus e staining pattern, Reversal of the AR effect by 14HRR or retinol indicates that F-actin is a common site for regulation by retro-retinoids, Inhibitio n of both cell death and actin depolymerisation by bcl-2 implies that cytos keleton reorganization is downstream of bcl-2-related processes. Furthermor e, stabilization of microfilaments by jasplakinolide increased the survival potential of AR treated cells, while weakening the cytoskeleton by cytocha lasin B abetted apoptosis. Thus the cytoskeleton is an important way statio n in a communication network that decides whether a cell should live or die .