RRC ID 54876
Author Tabei Y, Fukui H, Nishioka A, Hagiwara Y, Sato K, Yoneda T, Koyama T, Horie M.
Title Effect of iron overload from multi walled carbon nanotubes on neutrophil-like differentiated HL-60 cells.
Journal Sci Rep
Abstract Multi walled carbon nanotubes (MWCNTs) are one of the most intensively explored nanomaterials because of their unique physical and chemical properties. Due to the widespread use of MWCNTs, it is important to investigate their effects on human health. The precise mechanism of MWCNT toxicity has not been fully elucidated. The present study was designed to examine the mechanisms of MWCNT toxicity toward human promyelocytic leukemia HL-60 cells. First, we found that MWCNTs decreased the viability of neutrophil-like differentiated HL-60 cells but not undifferentiated HL-60 cells. Because neutrophil-like differentiated HL-60 cells exhibit enhanced phagocytic activity, the cytotoxicity of MWCNTs is dependent on the intracellularly localized MWCNTs. Next, we revealed that the cytotoxicity of MWCNTs is correlated with the intracellular accumulation of iron that is released from the engulfed MWCNTs in an acidic lysosomal environment. The intracellular accumulation of iron was repressed by treatment with cytochalasin D, a phagocytosis inhibitor. In addition, our results indicated that iron overload enhanced the release of interleukin-8 (IL-8), a chemokine that activates neutrophils, and subsequently elevated intracellular calcium concentration ([Ca2+]i). Finally, we found that the sustained [Ca2+]i elevation resulted in the loss of mitochondrial membrane potential and the increase of caspase-3 activity, thereby inducing apoptotic cell death. These findings suggest that the iron overload caused by engulfed MWCNTs results in the increase of IL-8 production and the elevation of [Ca2+]i, thereby activating the mitochondria-mediated apoptotic pathway.
Volume 9(1)
Pages 2224
Published 2019-2-18
DOI 10.1038/s41598-019-38598-4
PII 10.1038/s41598-019-38598-4
PMID 30778158
PMC PMC6379482
MeSH Apoptosis Calcium / metabolism Cell Differentiation* Cell Survival Flow Cytometry HL-60 Cells Humans Interleukin-8 / biosynthesis Iron / chemistry Iron / metabolism* Iron Overload / etiology* Iron Overload / metabolism* Iron Overload / pathology Nanotubes, Carbon* / chemistry Nanotubes, Carbon* / toxicity Neutrophils / cytology* Neutrophils / metabolism*
IF 4.011
Times Cited 6
Human and Animal Cells HL-60(RCB3683)