In this study we examined interactions between human dermal fibroblasts and chromium acetate hydroxide originating from environmental waste sediments. We show that initially exposure of fibroblasts to Cr (III) induced membrane-dependent signaling including activation of Rac1 GTPase, Src and apoptosis signal-regulating kinase 1 (ASK-1) kinases leading to increased activities of p38 and particularly Jun N-terminal kinase (JNK) and subsequent activation of caspase-3. At later treatment intervals (48-96 h), caspase-3 activity became suppressed and markedly increased lactate dehydrogenase (LDH) release was observed. Further experiments demonstrated that LDH release occurred in the presence of increased oxidative stress, extensive DNA damage, overactivation of poly(ADP-ribose)polymerase-1 (PARP-1) and depletion of ATP. Using specific inhibitors it was demonstrated that oxidative stress along with PARP-1 activity are responsible for cell death mode switch and upon their inhibition caspase-3 activity could be restored. In conclusion, Cr (III) seems to induce a biphasic response in dermal fibroblasts, with initial apoptosis switched to necrosis via increased DNA damage and resulting PARP-1 activity.

• MeSH
• acetáty toxicita   MeSH
• adenosintrifosfát metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buněčná smrt genetika   účinky léků   MeSH
• buněčné linie MeSH
• chrom toxicita   MeSH
• ELISA MeSH
• fibroblasty enzymologie   metabolismus   patologie   účinky léků   MeSH
• kaspasa 3 biosyntéza   metabolismus   MeSH
• kůže cytologie   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• odpadky - odstraňování MeSH
• oxidační stres účinky léků   genetika   MeSH
• poly(ADP-ribosa)polymerasy biosyntéza   metabolismus   MeSH
• poškození DNA MeSH
• proliferace buněk účinky léků   MeSH
• rac1 protein vázající GTP biosyntéza   metabolismus   MeSH
• skupina kinas odvozených od src-genu biosyntéza   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH