PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport.
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 a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3744505?pdf=render |
| _version_ | 1818511190500835328 |
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| author | Farshad Tamari Fannie W Chen Chunlei Li Jagrutiben Chaudhari Yiannis A Ioannou |
| author_facet | Farshad Tamari Fannie W Chen Chunlei Li Jagrutiben Chaudhari Yiannis A Ioannou |
| author_sort | Farshad Tamari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T23:30:03Z |
| format | Article |
| id | doaj.art-b7aa6a06a22c4d90a7a8d55f022b978b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T23:30:03Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b7aa6a06a22c4d90a7a8d55f022b978b2022-12-22T01:29:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7416910.1371/journal.pone.0074169PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport.Farshad TamariFannie W ChenChunlei LiJagrutiben ChaudhariYiannis A IoannouActivation 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.http://europepmc.org/articles/PMC3744505?pdf=render |
| spellingShingle | Farshad Tamari Fannie W Chen Chunlei Li Jagrutiben Chaudhari Yiannis A Ioannou PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport. PLoS ONE |
| title | PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport. |
| title_full | PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport. |
| title_fullStr | PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport. |
| title_full_unstemmed | PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport. |
| title_short | PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport. |
| title_sort | pkc activation in niemann pick c1 cells restores subcellular cholesterol transport |
| url | http://europepmc.org/articles/PMC3744505?pdf=render |
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