Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cadmium-induced cell death is associated with endoplasmic reticulum (ER) stress. We previously found that inhibition of FBXO6 expression, which is a ubiquitin ligase involved in ER-associated protein degradation (ERAD), induces high sensitivity to cadmium in HEK293 cells. However, the precise role of FBXO6 in ER stress remains unexplored. In this study, we investigated the role of FBXO6 in cadmium-induced ER stress in HEK293 cells. Our results showed that the cadmium-induced increase in expression of the ER stress marker proteins, BiP and CHOP, was further enhanced by inhibiting FBXO6 expression. Cadmium-induced c-Jun phosphorylation was also markedly increased by inhibition of FBXO6 expression. However, this c-Jun phosphorylation was almost entirely abolished by inhibition of c-Jun N-terminal kinase 1 (JNK1) expression. The level of high cadmium sensitivity induced by inhibition of FBXO6 expression was markedly lower in the JNK1-ablated cells than in the control cells. In addition, cadmium elevated the cellular level of ERAD substrate proteins, and this elevation was further enhanced by inhibiting FBXO6 expression. These results suggest that FBXO6 might inhibit cadmium-induced ER stress by functioning as a ubiquitin ligase in the ERAD system, thereby attenuating the cell death induced by subsequent JNK1 activation.
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PMID:FBXO6 attenuates cadmium toxicity in HEK293 cells by inhibiting ER stress and JNK activation. 2537 77

At present, there are no reports on the relationship between fluoride-induced apoptosis and endoplasmic reticulum (ER) stress (ER stress) in the spleen of human and animals in vivo and in vitro. Therefore, the aim of this study was to define sodium fluoride (NaF)-induced apoptosis mediated by ER stress in the spleen of mice in vivo and in vitro. Apoptosis and expression levels of the ER stress-related proteins were detected by flow cytometry and western blot, respectively. The results showed that NaF treatment increased lymphocytes apoptosis, which was consistent with NaF-caused ER Stress. NaF-caused ER stress was characterized by up-regulating protein expression levels of glucose-regulated protein 78 (BiP) and glucose-regulated protein 94 (GRP94), and by activating unfolded protein response (UPR). The signaling pathway of ER stress-associated apoptosis was activated by up-regulating protein expression levels of cleaved cysteine aspartate specific protease-12 (cleaved caspase-12), growth arrest and DNA damage-inducible gene 153 (Gadd153/CHOP) and phosphorylation of JUN N-terminal kinase (p-JNK). Additionally, our in vitro study found that apoptotic rate was decreased with remarkable down-regulation of the cleaved caspase-12, CHOP, p-JNK after ER stress was inhibited by 4-Phenylbutyric acid (4-PBA) treatment. In conclusion, NaF-induced apoptosis may mediated by ER stress in the spleen.
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PMID:Sodium fluoride (NaF) induces the splenic apoptosis via endoplasmic reticulum (ER) stress pathway in vivo and in vitro. 2803 91