Endoplasmic reticulum stress associated with lead (Pb)-induced olfactory epithelium toxicity in an olfactory dark basal cell line.

Lead (Pb) can damage organs and also have undesirable effects on neural development. To explore the effects of Pb on olfactory cells, we investigated Pb-induced cell toxicity in the DBC1.2 olfactory cell line, with a focus on endoplasmic reticulum (ER) stress, apoptosis, and necroptosis. Representative markers of ER stress, apoptosis, and necroptosis were analyzed by quantitative PCR. The mRNA expression levels of GRP94, GRP78, spliced XBP1, PERK, and ATF6 increased significantly after Pb exposure in a dose-dependent manner. The expression of Caspase 3 and Caspase 12 did not increase after Pb exposure, which suggested that apoptosis-induced cell death was not activated after Pb exposure. However, the mRNA of RIPK3 and MLKL showed increases in expression, which indicated that necroptosis-induced cell death was activated after Pb exposure. These results indicate that Pb exposure induced dose-dependent cytotoxicity through ER stress and necroptosis pathways in DBC1.2 cells, whereas the apoptosis pathway was not significantly stimulated. HEPES buffer showed a partial protective effect in terms of ER stress, apoptosis, and necroptosis. In summary, the necroptosis pathway plays a crucial rule in Pb exposure-induced cytotoxicity in olfactory cells.
(© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)