N-Nitrosodimethylamine induced lung fibroblast cell death is associated with JNK activation

N-Nitrosodialkylamines are considered a potential health hazard for humans. Among various N-nitrosodialkylamines compound, N-nitrosodimethylamine (NDMA), was applied to lung cells, MLG. In order to examine the effect of NDMA in lung cells, cell death was first examined. NDMA induced cell death in a dose-dependent manner. Mitogen activated protein kinase (MAPK) involvement was tested using SP600125 for JNK, SB203580 for P38 MAPK, or PD98059 for ERK. SP compound induced a significant reduction of cell death, compared with other inhibitors. NDMA induced an increase in expression of ER stress response proteins, including GRP78, IRE-1 alpha, CHOP, GRP94, p-eIF2 alpha, p-JNK, or sXBP-1. Pretreatment with SP compound regulated expression of CHOP, the transcription factor associated with proapoptotic gene induction. This study showed that NDMA-induced cell death was resulted due to JNK activation. ER stress was also induced in the toxic situations. Study of the meaning of ER stress will be necessary in the near future.