| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5863067 | Toxicology in Vitro | 2012 | 8 Pages |
Nickel compounds are potential carcinogenic agents that produce a range of biological effects, including inhibition of cell death. Because suppression of apoptosis is thought to contribute to the initiation of carcinogenesis, we investigated the effects of nickel acetate (Ni2+) treatment on apoptosis in two different airway epithelial cell lines (A549 and Beas-2B, respectively). Furthermore, since both the epidermal growth factor receptor (EGFR) and neuregulin (Neu) are involved in neoplastic development, mRNAs and expression levels of total and phosphorylated proteins (p-EGFRTyr1173 and p-NeuTyr1248, respectively) were also measured. We found that exposure of A549 cells to Ni2+ resulted in significantly reduced cell viability, as well as increased apoptosis and DNA fragmentation at relatively low concentrations (0.1 and 0.5Â mM) after 24 and 48Â h. These changes were accompanied by reduced EGFR and Neu mRNAs and proteins, phosphorylated proteins as well as decreased Bcl-2 and increased BAX protein expression. Conversely, Beas-2B cells exposed to equivalent concentrations of Ni2+ did not show evident signs of apoptosis and DNA damage, hence showing increased expression and phosphorylation of both EGFR and Neu, increased Bcl-2 and reduced BAX expression. Altogether, our finding indicate that Ni2+ exposure differently affects apoptosis initiation either in non-tumorigenic (Beas-2B) and tumorigenic airway epithelial cells (A549), suggesting a potential involvement of EGFR/Neu receptors.
⺠Beas-2B are less susceptible than A549 cells to Ni2+-induced apoptosis. ⺠Ni2+ exposure differently regulates EGFR/Neu activation in the two cell lines. ⺠EGFR/Neu expression and activation is increased in Ni2+-exposed Beas-2B but not in A549 cells. ⺠EGFR/Neu activation is correlated with increased Bcl-2 and reduced BAX levels.
