Endoplasmic reticulum stress is involved in N-methyl-N'-nitro-N-nitrosoguanidine, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide and mitomycin-induced cellular response in FL cells / 中国病理生理杂志

ABSTRACT

AIM: To understand whether endoplasmic reticulum stress (ER-stress) is involved in DNA-damaging agent/carcinogen induced cell responses. METHODS: Three DNA-damaging agents/carcinogens different in the mode of action, ie, alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine (MNNG), bulky adduct forming agent benzo[a] pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE) and cross-linking agent mitomycin C (MMC) were selected. SDS-PAGE and immunoblotting were used to examine the protein levels of GRP78/BiP, GDADD153/CHOP and activation state of endoplasmic reticulum located caspase-12 in FL cells before and after MNNG, BPDE or MMC exposure. RESULTS: Immunoblotting showed that the protein level of endoplasmic reticulum specific proteins GRP78/BiP and GADD153/CHOP were significantly increased and endoplasmic reticulum located caspase-12 was activated in low concentration of MNNG (0.25 and 1 ?mol/L) and BPDE (5 and 50 nmol/L)-treated cells. MMC at all of the three concentration used (5, 50 and 500 ?mol/L) decreased the expression of GRP78/BiP, while it has no effects on CHOP and caspase-12. CONCLUSIONS: Both low concentration MNNG and BPDE could trigger the ER-stress in the exposed cells, while MMC could induce the down-regulation of the GRP78/BiP protein, which plays an important mediating role in the induction of ER-stress and may thus change the responsiveness against ER-stress inducers. It is suggested that ER-stress might partially mediate the cellular responses excited by exposure to some DNA-damaging agents/carcinogens.