ArticlePloS one2013
PKC activation in Niemann pick C1 cells restores subcellular cholesterol transport.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Global Proteomics for Identifying the Alteration Pathway of Niemann-Pick Disease Type C Using Hepatic Cell Models.International journal of molecular sciences · 2023Article
- Trimethylene Methane Dianion Equivalent for the Asymmetric Consecutive Allylation of Aldehydes: Applications to Prins-Driven Macrocyclizations for the Synthesis of Bryostatin 1 and Analogues.The Journal of organic chemistry · 2022Article
- Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.International journal of molecular sciences · 2021Review
- Function-Oriented Synthesis: Design, Synthesis, and Evaluation of Highly Simplified Bryostatin Analogues.The Journal of organic chemistry · 2020Article
- Mass spectrometry imaging and LC/MS reveal decreased cerebellar phosphoinositides in Niemann-Pick type C1-null mice.Journal of lipid research · 2020Article
- Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy.Nature communications · 2020Article
- Alteration of GABAergic Input Precedes Neurodegeneration of Cerebellar Purkinje Cells of NPC1-Deficient Mice.International journal of molecular sciences · 2019Article
- Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of NPC1-deficient Mice.Scientific reports · 2018Article
- Activation of PKC triggers rescue of NPC1 patient specific iPSC derived glial cells from gliosis.Orphanet journal of rare diseases · 2017Article
- Molecular dynamics simulations reveal ligand-controlled positioning of a peripheral protein complex in membranes.Nature communications · 2017Article
- Protein Kinase C-α is a Critical Protein for Antisense Oligonucleotide-mediated Silencing in Mammalian Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Immune dysfunction in Niemann-Pick disease type C.Journal of neurochemistry · 2016Review
- Smad2/3 Upregulates the Expression of Vimentin and Affects Its Distribution in DBP-Exposed Sertoli Cells.PPAR research · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
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