Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracts of human liver were found to contain activities which copurified and coeluted with the two major subtypes of mediators (type A and type P) isolated from insulin-stimulated rat liver. The putative type A mediator from human liver inhibited cAMP-dependent protein kinase from bovine heart, decreased phosphoenolypyruvate carboxykinase mRNA levels in rat hepatoma cells, and stimulated lipogenesis in rat adipocytes. The putative type P mediator stimulated bovine heart pyruvate dehydrogenase phosphatase. Both fractions were able to stimulate proliferation of EGFR T17 fibroblasts and the type A was able to support growth in organotypic cultures of chicken embryo cochleovestibular ganglia. Both activities were resistant to Pronase treatment and the presence of carbohydrates, phosphate, and free-amino groups were confirmed in the two fractions. These properties are consistent with the structure/ function characteristics of the type A and P inositolphosphoglycans (IPG) previously characterized from rat liver. Further, the ability of the human-derived mediators to interact with rat adipocytes and bovine-derived metabolic enzymes suggests similarity in structure between the mediators purified from different species. Galactose oxidase-susceptible membrane-associated glycosylphosphatidylinositols (GPI) have been proposed to be the precursors of IPG. GPI was purified from human liver membranes followed by treatment with galactose oxidase and reduction with NaB3H4. Serial t.l.c. revealed three radiolabeled bands which comigrated with the putative GPI precursors found in rat liver. These galactose-oxidase-reactive lipidic compounds, however, were only partially susceptible to hydrolysis with phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis and were resistant to glycosylphosphatidylinositol-specific phospholipase C from Trypanosoma brucei. These data indicate that IPG molecules with insulin-like biological activities are present in human liver.
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PMID:Isolation and partial characterisation of insulin-mimetic inositol phosphoglycans from human liver. 925 87

Liver cancer is one of the most common malignancies worldwide. The RAF kinase inhibitors are effective in the treatment of hepatocellular carcinoma (HCC); therefore, inhibition of the BRAF/MEK/ERK pathway has become a new therapeutic strategy for novel HCC therapy. However, targeted specific delivery systems for tumors are still significant obstacle to clinical applications. Galactose (GAL) can target the asialoglycoprotein receptor (ASGPR) that is highly expressed on liver cancer cells. In this study, we designed a novel multifunctional nanomaterial GAL-GNR-siBRAF which consists of three parts, GAL as the liver cancer-targeting moiety, golden nanorods (GNR) offering photothermal capability under near infrared light, and siRNA specifically silencing BRAF (siBRAF). The nanocarrier GAL-GNR-siBRAF showed high siRNA loading capacity and inhibited the degradation of siRNA in serum. Compared with naked gold nanorods, GAL-GNR-siBRAF possessed lower biotoxicity and higher efficacy of gene silencing. Treatment with GAL-GNR-siBRAF significantly downregulated the expression of BRAF and impaired proliferation, migration, and invasion of liver cancer cells. Moreover, combinatorial photothermal effects and BRAF knockdown by GAL-GNR-siBRAF effectively given rise to tumor cell death. Therefore, our study developed a new type of targeted multi-functional nanomaterial GAL-GNR-siBRAF for the treatment of liver cancer, which provides ideas for the development of new clinical treatment methods.
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PMID:Targeted Gene Silencing BRAF Synergized Photothermal Effect Inhibits Hepatoma Cell Growth Using New GAL-GNR-siBRAF Nanosystem. 3244 85