TY - JOUR
T1 - Endoplasmic reticulum stress signaling is involved in silver nanoparticles-induced apoptosis
AU - Zhang, Rui
AU - Piao, Mei Jing
AU - Kim, Ki Cheon
AU - Kim, Areum Daseul
AU - Choi, Jeong Yun
AU - Choi, Jinhee
AU - Hyun, Jin Won
PY - 2012/1
Y1 - 2012/1
N2 - Although silver nanoparticles (AgNPs) have been reported to exert strong acute toxic effects on various cultured cells by inducing oxidative stress, the molecular mechanisms by which AgNPs-damaged cells are unknown. Because the endoplasmic reticulum (ER) may play an important role in the response to oxidative stress-induced damage and is quite sensitive to oxidative damage, we hypothesized that AgNPs may exert cytotoxic effects on cells by modulating ER stress. In our study, AgNPs resulted in cytotoxicity and apoptotic cell death when analyzing cell viability, DNA fragmentation and the apoptotic sub-G 1 population. Flow cytometry and confocal microscopy indicated that the cells were sensitive to AgNPs with respect to the induction of mitochondrial Ca 2+ overloading and enhancement of ER stress. AgNPs induced a number of signature ER stress markers, including phosphorylation of RNA-dependent protein kinase-like ER kinase (PERK) and its downstream eukaryotic initiation factor 2α, phosphorylation of inositol-requiring protein 1 (IRE1), splicing of ER stress-specific X-box transcription factor-1, cleavage of activating transcription factor 6 (ATF6) and up-regulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153). Down-regulation of PERK, IRE1 and ATF6 expression using siRNA significantly decreased AgNPs-induced the enhancement of ER stress. In addition, down-regulation of CHOP expression with siRNA CHOP attenuated AgNPs-induced apoptosis. Taken together, the present study supports an important role for the ER stress response in mediating AgNPs-induced apoptosis.
AB - Although silver nanoparticles (AgNPs) have been reported to exert strong acute toxic effects on various cultured cells by inducing oxidative stress, the molecular mechanisms by which AgNPs-damaged cells are unknown. Because the endoplasmic reticulum (ER) may play an important role in the response to oxidative stress-induced damage and is quite sensitive to oxidative damage, we hypothesized that AgNPs may exert cytotoxic effects on cells by modulating ER stress. In our study, AgNPs resulted in cytotoxicity and apoptotic cell death when analyzing cell viability, DNA fragmentation and the apoptotic sub-G 1 population. Flow cytometry and confocal microscopy indicated that the cells were sensitive to AgNPs with respect to the induction of mitochondrial Ca 2+ overloading and enhancement of ER stress. AgNPs induced a number of signature ER stress markers, including phosphorylation of RNA-dependent protein kinase-like ER kinase (PERK) and its downstream eukaryotic initiation factor 2α, phosphorylation of inositol-requiring protein 1 (IRE1), splicing of ER stress-specific X-box transcription factor-1, cleavage of activating transcription factor 6 (ATF6) and up-regulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153). Down-regulation of PERK, IRE1 and ATF6 expression using siRNA significantly decreased AgNPs-induced the enhancement of ER stress. In addition, down-regulation of CHOP expression with siRNA CHOP attenuated AgNPs-induced apoptosis. Taken together, the present study supports an important role for the ER stress response in mediating AgNPs-induced apoptosis.
KW - Apoptosis
KW - CCAAT/enhancer-binding protein-homologous protein
KW - Endoplasmic reticulum stress
KW - Oxidative stress
KW - Silver nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=83555175982&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2011.10.019
DO - 10.1016/j.biocel.2011.10.019
M3 - Article
C2 - 22064246
AN - SCOPUS:83555175982
SN - 1357-2725
VL - 44
SP - 224
EP - 232
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 1
ER -