| RRC ID |
74573
|
| 著者 |
Naranmandura H, Xu S, Koike S, Pan LQ, Chen B, Wang YW, Rehman K, Wu B, Chen Z, Suzuki N.
|
| タイトル |
The endoplasmic reticulum is a target organelle for trivalent dimethylarsinic acid (DMAIII)-induced cytotoxicity.
|
| ジャーナル |
Toxicol Appl Pharmacol
|
| Abstract |
The purpose of present study was to characterize the endoplasmic reticulum stress and generation of ROS in rat liver RLC-16 cells by exposing to trivalent dimethylarsinous acid (DMAIII) and compared with that of trivalent arsenite (iAsIII) and monomethylarsonous acid (MMAIII). Protein kinase-like endoplasmic reticulum kinase (PERK) phosphorylation was significantly induced in cells exposed to DMAIII, while there was no change in phosphorylated PERK (P-PERK) detected in cells after exposure to iAsIII or MMAIII. The generation of reactive oxygen species (ROS) after DMAIII exposure was found to take place specifically in the endoplasmic reticulum (ER), while previous reports showed that ROS was generated in mitochondria following exposure to MMAIII. Meanwhile, cycloheximide (CHX) which is an inhibitor of protein biosynthesis strongly inhibited the DMAIII-induced intracellular ROS generation in the ER and the phosphorylation of PERK, suggesting the induction of ER stress probably occurs through the inhibition of the protein folding process. Activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) mRNA were induced by all three arsenic species, however, evidence suggested that they might be induced by different pathways in the case of iAsIII and MMAIII. In addition, ER resident molecular chaperone glucose-regulated protein78 (GRP78) was not affected by trivalent arsenicals, while it was induced in positive control only at high concentration (Thapsigargin;Tg), suggesting the GRP78 is less sensitive to low levels of ER stress. In summary, our findings demonstrate that the endoplasmic reticulum is a target organelle for DMAIII-induced cytotoxicity.
|
| 巻・号 |
260(3)
|
| ページ |
241-9
|
| 公開日 |
2012-5-1
|
| DOI |
10.1016/j.taap.2012.02.017
|
| PII |
S0041-008X(12)00083-X
|
| PMID |
22425709
|
| MeSH |
Activating Transcription Factor 4 / metabolism
Animals
Arsenites / toxicity*
Cacodylic Acid / toxicity*
Cell Line
Endoplasmic Reticulum / drug effects
Endoplasmic Reticulum / metabolism
Endoplasmic Reticulum Stress / drug effects*
Heat-Shock Proteins / metabolism
Liver / cytology
Liver / drug effects
Liver / metabolism
Organometallic Compounds / toxicity*
Phosphorylation / drug effects
Protein Folding / drug effects
RNA, Messenger / metabolism
Rats
Reactive Oxygen Species / metabolism*
Transcription Factor CHOP / metabolism
eIF-2 Kinase / metabolism
|
| IF |
4.421
|
| リソース情報 |
| ヒト・動物細胞 |
RLC-16 |
