Distinct autophagy-apoptosis related pathways activated by Multi-walled (NM 400) and Single-walled carbon nanotubes (NIST-SRM2483) in human bronchial epithelial (16HBE14o-) cells.

ABSTRACT

Given the recent development in the field of particle and fibre toxicology, parallels have been drawn between Carbon nanotubes (CNTs) and asbestos. It is now established that both multi-walled (MWCNTs) and single-walled (SWCNTs) carbon nanotubes might contribute to pulmonary disease. Although multiple mechanisms might be involved in CNT induced pathogenesis, systematic understanding of the relationship between different CNT exposure (MWCNT vs SWCNT) and autophagy/ apoptosis/ necrosis, in human lung epithelial cells remains limited. In this study, we demonstrate that exposure to MWCNT (NM-400), but not SWCNT (NIST-SRM2483), leads to an autophagic response after acute exposure (24 h). MWCNT exposure was characterized by an increase in anti-apoptotic BCL2, downregulation of executor Caspase-3/7 and increase in expression of genes from the autophagy machinery. For SWCNT exposure however, we observed an overexpression of executor Caspase-3/7 and upregulation of pro-apoptotic BAX; enrichment for processes like cornification, apoptotic process, cell differentiation from proteomic analysis. These results clearly indicate a major difference in the pathways initiated by the CNTs, in vitro. While the present study design provides mechanistic understanding after an acute exposure for the tested CNTs, we believe that the information obtained here would have relevance in better understanding of CNT toxicity and pathogenesis in general.