PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport
| العنوان: | PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport |
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| المؤلفون: | Fannie W. Chen, Farshad Tamari, Yiannis A. Ioannou, Jagrutiben Chaudhari, Chunlei Li |
| المصدر: | PLoS ONE, Vol 8, Iss 8, p e74169 (2013) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Cell Extracts, congenital, hereditary, and neonatal diseases and abnormalities, lcsh:Medicine, Vimentin, CHO Cells, 03 medical and health sciences, Enzyme activator, Cricetulus, 0302 clinical medicine, Cricetinae, hemic and lymphatic diseases, Animals, lcsh:Science, Protein Kinase C, Protein kinase C, 030304 developmental biology, Sphingolipids, 0303 health sciences, Multidisciplinary, Esterification, biology, Activator (genetics), Fatty Acids, lcsh:R, nutritional and metabolic diseases, Biological Transport, Niemann-Pick Disease, Type C, Sphingolipid, 3. Good health, Cell biology, Enzyme Activation, Cholesterol, Phenotype, Endocytic vesicle, Solubility, Biochemistry, rab GTP-Binding Proteins, biology.protein, lipids (amino acids, peptides, and proteins), lcsh:Q, NPC1, Cholesterol storage, 030217 neurology & neurosurgery, Research Article |
| الوصف: | Activation of protein kinase C (PKC) has previously been shown to ameliorate the cholesterol transport defect in Niemann Pick Type C1 (NPC1) cells, presumably by increasing the soluble levels of one of its substrates, vimentin. This activity would then restore the vimentin cycle in these cells and allow vimentin-dependent retrograde transport to proceed. Here, we further investigate the effects of PKC activation in NPC1 cells by evaluating different isoforms for their ability to solubilize vimentin and correct the NPC1 cholesterol storage phenotype. We also examine the effects of PKC activators, including free fatty acids and the PKC-specific activator diazoxide, on the NPC1 disease phenotype. Our results indicate that PKC isoforms α, βII, and ε have the greatest effects on vimentin solubilization. Furthermore, expression or activation of PKCε in NPC1 cells dramatically reduces the amount of stored cholesterol and restores cholesterol transport out of endocytic vesicles. These results provide further support for the contribution of PKCs in NPC1 disease pathogenesis and suggest that PKCs may be targeted in future efforts to develop therapeutics for NPC1 disease. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cd7b5081ebc67129845bea53c37a017 http://europepmc.org/articles/PMC3744505?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0cd7b5081ebc67129845bea53c37a017 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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