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 microM) 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.
Rudolf
Emil
E
Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Simkova 870, 500 38 Hradec Kralove, Czech Republic. rudolf@lfhk.cuni.cz
Cervinka
Miroslav
M
Cerman
Jaroslav
J
Schroterova
Ladislava
L
D000199:Actins / Q000737:chemistry* / Q000187:drug effects*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D003599:Cytoskeleton / Q000737:chemistry* / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D012867:Skin / Q000166:cytology / Q000187:drug effects*
D000199:Actins; D015415:Biomarkers; D002857:Chromium; C074702:chromium hexavalent ion; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases