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)

Accumulation of saturated fatty acids in the liver can cause nonalcoholic fatty liver disease (NAFLD). This study investigated saturated fatty acid induction of endoplasmic reticulum (ER) stress and apoptosis in human liver cells and the underlying causal mechanism. Human liver L02 and HepG2 cell lines were exposed to the saturated fatty acid sodium palmitate. MTT assay was used for cell viability, flow cytometry and Hoechst 33258 staining for apoptosis, RT-PCR for mRNA expression, and Western blot for protein expression. Silence of PRK-like ER kinase (PERK) expression in liver cells was through transient transfection of PERK shRNA. Treatment of L02 and HepG2 cells with sodium palmitate reduced cell viability through induction of apoptosis. Sodium palmitate also induced ER stress in the cells, indicated by upregulation of PERK phosphorylation and expression of BiP, ATF4, and CHOP proteins. Sodium palmitate had little effect on activating XBP-1, a common target of the other two canonical sensors of ER stress, ATF6, and IRE1. Knockdown of PERK gene expression suppressed the PERK/ATF4/CHOP signaling pathway during sodium palmitate-induced ER stress and significantly inhibited sodium palmitate-induced apoptosis in L02 and HepG2 cells. Saturated fatty acid-induced ER stress and apoptosis in these human liver cells were enacted through the PERK/ATF4/CHOP signaling pathway. Future study is warranted to investigate the role of these proteins in mediating saturated fatty acid-induced NAFLD in animal models.
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PMID:Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway. 2224 6

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, characterized by a high degree of malignancy, a poor prognosis, and chemotherapy resistance. The anticancer activities of cantharidin and its derivatives have been widely reported. Sodium demethylcantharidate is a derivative of cantharidin that shows excellent anticancer activity against multiple types of cancer, including HCC. However, its mechanism of action remains unclear. We evaluated the anticancer activities of sodium demethylcantharidate in SMMC-7721 and Bel-7402 HCC cells in the current study and demonstrated that sodium demethylcantharidate effectively inhibited the proliferation of SMMC-7721 and Bel-7402 HCC cells in a dose- and time-dependent manner. Flow cytometry analysis showed that sodium demethylcantharidate could induce apoptosis. Western blotting revealed that endoplasmic reticulum (ER) stress-related proteins (p-IRE1, GRP78/BiP, CHOP, the spliced form of XBP1, and caspase-12) were upregulated in SMMC-7721 and Bel-7402 cells after exposure to sodium demethylcantharidate. Based on those results, we confirmed that sodium demethylcantharidate could induce apoptosis via ER stress. Moreover, a significant attenuation of SMMC-7721 cell tumorigenesis was observed after sodium demethylcantharidate treatment in a nude mouse xenograft model. These findings elucidate one mechanism underlying the anticancer activity of sodium demethylcantharidate against HCC.
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PMID:Sodium demethylcantharidate induces apoptosis in hepatocellular carcinoma cells via ER stress. 3121 84