Beryllium is an inhibitor of cellular GSK-3β that is 1,000-fold more potent than lithium
| Autor: | Ataur Rahman Mohammed Abdul, Ronald K. Gary, Priyatham Gorjala, Swapna R. Mudireddy |
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| Rok vydání: | 2014 |
| Předmět: |
Beryllium sulfate
macromolecular substances Real-Time Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Cell Line Biomaterials Glycogen Synthase Kinase 3 Phosphoserine chemistry.chemical_compound GSK-3 Cell Line Tumor Fluorescence Resonance Energy Transfer Humans RNA Messenger Phosphorylation Kinase activity Protein Kinase Inhibitors GSK3B Glycogen Synthase Kinase 3 beta Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Kinase Chemistry Metals and Alloys Fibroblasts Recombinant Proteins Cell biology Biochemistry Cell culture Lithium chloride Beryllium Glioblastoma Lithium Chloride General Agricultural and Biological Sciences |
| Zdroj: | BioMetals. 27:1203-1216 |
| ISSN: | 1572-8773 0966-0844 |
| Popis: | Glycogen synthase kinase 3β (GSK-3β) is a key regulator in signaling networks that control cell proliferation, metabolism, development, and other processes. Lithium chloride is a GSK-3 family inhibitor that has been a mainstay of in vitro and in vivo studies for many years. Beryllium salt has the potential to act as a lithium-like inhibitor of GSK-3, but it is not known whether this agent is effective under physiologically relevant conditions. Here we show that BeSO4 inhibits endogenous GSK-3β in cultured human cells. Exposure to 10 µM Be(2+) produced a decrease in GSK-3β kinase activity that was comparable to that produced by 10 mM Li(+), indicating that beryllium is about 1,000-fold more potent than the classical inhibitor when treating intact cells. There was a statistically significant dose-dependent reduction in specific activity of GSK-3β immunoprecipitated from cells that had been treated with either agent. Lithium inhibited GSK-3β kinase activity directly, and it also caused GSK-3β in cells to become phosphorylated at serine-9 (Ser-9), a post-translational modification that occurs as part of a well-known positive feedback loop that suppresses the kinase activity. Beryllium also inhibited the kinase directly, but unlike lithium it had little effect on Ser-9 phosphorylation in the cell types tested, suggesting that alternative modes of feedback inhibition may be elicited by this agent. These results indicate that beryllium, like lithium, can induce perturbations in the GSK-3β signaling network of treated cells. |
| Databáze: | OpenAIRE |
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