title: Multiwalled carbon nanotubes activate NF-κB and AP-1 signaling pathways to induce apoptosis in rat lung epithelial cells.
abstract: Our previous report on multiwall carbon nanotubes (MWCNT) has demonstrated the generation of reactive radicals and depletion of intracellular antioxidants which in turn cause cell death through activation of caspases. The molecular mechanism of cellular death due to MWCNT is not clear yet. In this study, we investigated the signaling pathways implicated in MWCNT-induced apoptosis in rat lung epithelial cells. First, we assessed the DNA damage in response to MWCNT treatment and showed the significant DNA damage as compared to control. The collapse of the mitochondrial membrane integrity, release of cytochrome c into the cytosol, reduction in cellular ATP content, increased levels of mitochondrial apoptogenic factor and activation and nuclear translocation of NF-κB were observed in MWCNT treated cells. In addition, a time-dependent induction of phosphorylated IκBα and its degradation were detected in cells exposed to MWCNT. Furthermore, MWCNT activated several death related proteins including apoptosis inducing factor, p53, p21 and bax. Together, our results suggest that signaling pathways such as NF-κB and AP-1 are activated upon MWCNT treatment for cellular cytotoxicity.
authors.affiliation: Molecular Toxicology Laboratory, Center for Biotechnology and Biomedical Sciences, Department of Biology, Norfolk State University, Norfolk, VA 23504, USA.
authors.forename: Prabakaran
authors.initials: P
authors.lastname: Ravichandran
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Baluchamy
authors.forename: Bindhu
authors.initials: B
authors.lastname: Sadanandan
authors.forename: Ramya
authors.initials: R
authors.lastname: Gopikrishnan
authors.forename: Santosh
authors.initials: S
authors.lastname: Biradar
authors.forename: Vani
authors.initials: V
authors.lastname: Ramesh
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Hall
authors.forename: Govindarajan T
authors.initials: GT
authors.lastname: Ramesh
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D002460:Cell Line; D045304:Cytochromes c / Q000032:analysis*; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects* / Q000502:physiology*; D008168:Lung / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D036103:Nanotechnology; D037742:Nanotubes, Carbon / Q000633:toxicity; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D051033:Apoptosis Inducing Factor; D016328:NF-kappa B; D037742:Nanotubes, Carbon; D018808:Transcription Factor AP-1; D025521:Tumor Suppressor Proteins; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D003576:Electron Transport Complex IV