Hexavalent chromium disrupts the actin cytoskeleton and induces mitochondria-dependent apoptosis in human dermal fibroblasts

Exposure to hexavalent chromium causes various adverse effects including deep skin ulcerations and allergic dermatitis. Because of many potential intracellular targets for hexavalent chromium toxicity, its mechanisms of action are not entirely understood. To investigate the role of the cytoskeleton and mitochondria in this process, primary human dermal fibroblasts were exposed to various concentrations of potassium chromate for 24 h. The followed markers included cell motility, cytoskeletal organization, oxidative stress, mitochondrial activity and activation of the apoptotic cascade. Potassium chromate (1.5-45 mu M) induced time- and. concentration-dependent cell shrinkage, reorganization of cytoskeleton and loss of motile activity in fibroblasts. In some cells this was followed by membrane blebbing. Dynamic changes in cell morphology were accompanied with the loss of mitochondrial membrane potential, increased oxidative stress and release of cytochrome c. Apoptosis was confirmed by detection of activated caspase-3 and nuclear fragmentation. The results indicate that in fibroblasts hexavalent chromium-induced damage to cytoskeleton and mitochondria might occur concurrently at relatively early stages of exposure. Furthermore, alterations of these targets seem to activate mitochondria-dependent and- independent apoptosis. (c) 2005 Elsevier Ltd. All rights reserved.