Protective Effects of SKF-96365, a Non-Specific Inhibitor of SOCE, against MPP+-Induced Cytotoxicity in PC12 Cells: Potential Role of Homer1
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{"title"=>"Protective Effects of SKF-96365, a Non-Specific Inhibitor of SOCE, against MPP+-Induced Cytotoxicity in PC12 Cells: Potential Role of Homer1", "type"=>"journal", "authors"=>[{"first_name"=>"Tao", "last_name"=>"Chen", "scopus_author_id"=>"56167761000"}, {"first_name"=>"Jie", "last_name"=>"Zhu", "scopus_author_id"=>"57198764139"}, {"first_name"=>"Chi", "last_name"=>"Zhang", "scopus_author_id"=>"56768382300"}, {"first_name"=>"Kai", "last_name"=>"Huo", "scopus_author_id"=>"55089265800"}, {"first_name"=>"Zhou", "last_name"=>"Fei", "scopus_author_id"=>"7005339154"}, {"first_name"=>"Xiao Fan", "last_name"=>"Jiang", "scopus_author_id"=>"7404626992"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84873161845", "doi"=>"10.1371/journal.pone.0055601", "pui"=>"368246919", "pmid"=>"23383239", "scopus"=>"2-s2.0-84873161845", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)"}, "id"=>"4e082512-5621-3a2f-871e-9553bf093295", "abstract"=>"Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized by loss of dopominergic (DA) neurons in substantia nigra pars compacta (SNpc), and can be experimentally mimicked by the neurotoxin MPP(+) in vitro models. In this study, we investigated the potential protective effect of SKF-96365, a non-specific inhibitor of SOCE (store-operated calcium entry), on MPP(+) induced cytotoxicity in PC12 cells. We found that pretreatment with SKF-96365 (10 µM and 50 µM) 30 min before injury significantly increased cell viability, decreased LDH release, prevented nuclear damage, and inhibited apoptotic cell death in MPP(+) stressed PC12 cells. The results of calcium image using the ratiometric calcium indicator Fura-2-AM also showed that SKF-96365 reduced the intracellular calcium overload induced by MPP(+) in PC12 cells. In addition, SKF-96365 decreased the expression of Homer1, a more recently discovered postsynaptic scaffolding protein with calcium modulating function, following MPP(+) administration in PC12 cells, while had no statistically significant effects on endoplasmic reticulum (ER) calcium concentration. Furthermore, overexpression of Homer1 by using recombinant lentivirus partly reversed protective effects of SKF-96365 against MPP(+) injury. The ER Ca(2+) release was further amplified and ER calcium recovery was delayed by Homer1 upregulation in PC12 cells following MPP(+) insult. Taken together, these data suggest that SKF-96365 protects PC12 cells against MPP(+) induced cytotoxicity, and this protection may be at least in part on the inhibition of intracellular calcium overload and suppression of Homer1-mediated ER Ca(2+) release.", "link"=>"http://www.mendeley.com/research/protective-effects-skf96365-nonspecific-inhibitor-soce-against-mppinduced-cytotoxicity-pc12-cells-po", "reader_count"=>11, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>1, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Belgium"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/497951"], "description"=>"<p>PC12 cells were transfected with lentivirus expressed Homer1 (LV-H1) or control lentivirus (LV-Con) for 72 h before MPP<sup>+</sup> insult, and the expression of Homer1 was examined by western blot analysis (A). The cell viability (B) and LDH release (C) were assayed 24 h later, and the Ca<sup>2+</sup> concentration in ER ([Ca<sup>2+</sup>]<sub>ER</sub>) was measured at 6, 12 and 18 min after MPP<sup>+</sup> insult (D), respectively. The data were represented as means ± SD from five experiments (A, B and C) or eight experiments (D). *<i>p</i><0.05 vs. control lentivirus (LV-Con), <sup>#</sup><i>p</i><0.05. and n.s., not statistically significant.</p>", "links"=>[], "tags"=>["homer1", "overexpression", "skf-96365-induced"], "article_id"=>168472, "categories"=>["Biotechnology", "Biochemistry", "Neuroscience", "Pharmacology"], "users"=>["Tao Chen", "Jie Zhu", "Chi Zhang", "Kai Huo", "Zhou Fei", "Xiao-fan Jiang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055601.g005", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_Homer1_overexpression_on_SKF_96365_induced_neuroprotection_/168472", "title"=>"Effect of Homer1 overexpression on SKF-96365-induced neuroprotection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:11:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/497820"], "description"=>"<p>PC12 cells were pretreated with 50 µM SKF-96365 or saline water (Vehicle) 30 min before MPP<sup>+</sup> insult, and the expression of Homer1 mRNA (A) or protein (B) was examined by real time RT-PCR or western blot analysis at 3 h, 6 h or 12 h, respectively. The Ca<sup>2+</sup> concentration in ER ([Ca<sup>2+</sup>]<sub>ER</sub>) was measured up to 21 min (C). After potentiating group I mGluR activity with selective agonist DHPG at 10 min, [Ca<sup>2+</sup>]<sub>ER</sub> was measured in MPP+-insulted PC12 cells with or without SKF-96365 (D). The data were represented as means ± SD from five experiments. *<i>p</i><0.05 vs. Vehicle group. n.s., not statistically significant.</p>", "links"=>[], "tags"=>["skf-96365", "homer1", "er"], "article_id"=>168333, "categories"=>["Biotechnology", "Biochemistry", "Neuroscience", "Pharmacology"], "users"=>["Tao Chen", "Jie Zhu", "Chi Zhang", "Kai Huo", "Zhou Fei", "Xiao-fan Jiang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055601.g004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_SKF_96365_on_Homer1_expression_and_ER_Ca_2_release_/168333", "title"=>"Effect of SKF-96365 on Homer1 expression and ER Ca<sup>2+</sup> release.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:10:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/497615"], "description"=>"<p>PC12 cells were pretreated with SKF-96365 in different concentrations (1 µM, 10 µM or 50 µM) 30 min before MPP<sup>+</sup> insult, and the cell viability (A) and LDH release (B) were assayed 24 h later. The data were represented as means ± SD from five experiments. <sup>#</sup><i>p</i><0.05 vs. control group and <sup>*</sup><i>p</i><0.05 vs. Vehicle group.</p>", "links"=>[], "tags"=>["skf-96365"], "article_id"=>168132, "categories"=>["Biotechnology", "Biochemistry", "Neuroscience", "Pharmacology"], "users"=>["Tao Chen", "Jie Zhu", "Chi Zhang", "Kai Huo", "Zhou Fei", "Xiao-fan Jiang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055601.g001", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_SKF_96365_on_MPP_induced_cytoxicity_/168132", "title"=>"Effect of SKF-96365 on MPP<sup>+</sup>-induced cytoxicity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:09:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/497678"], "description"=>"<p>PC12 cells were pretreated with 50 µM SKF-96365 or saline water (Vehicle) 30 min before MPP<sup>+</sup> insult, and stained with Hoechst 33342 (A) or PI (C) 24 h later. The number of Hoechst-positive (B) and PI-positive cells (D) were calculated, respectively. The number of cells in B1 (AV<sup>−</sup>/PI<sup>+</sup>, the necrotic cells), B2 (AV<sup>+</sup>/PI<sup>+</sup>, the late phase apoptotic cells), B3 (AV<sup>−</sup>/PI<sup>−</sup>, normal cells) and B4 (AV<sup>+</sup>/PI<sup>−</sup>, the early phase apoptotic cells) were also analyzed using Flow cytometry (E and F). The data were represented as means ± SD from five experiments. <sup>*</sup><i>p</i><0.05 vs. Vehicle group.</p>", "links"=>[], "tags"=>["skf-96365"], "article_id"=>168202, "categories"=>["Biotechnology", "Biochemistry", "Neuroscience", "Pharmacology"], "users"=>["Tao Chen", "Jie Zhu", "Chi Zhang", "Kai Huo", "Zhou Fei", "Xiao-fan Jiang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055601.g002", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_SKF_96365_on_MPP_induced_cell_death_/168202", "title"=>"Effect of SKF-96365 on MPP<sup>+</sup>-induced cell death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:10:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/497768"], "description"=>"<p>PC12 cells were pretreated with 50 µM SKF-96365 or saline water (Vehicle) 30 min before MPP<sup>+</sup> insult, and the intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>cyt</sub>) was measured up to 12 h. The data were represented as means ± SD from eight experiments. <sup>*</sup><i>p</i><0.05 and n.s., not statistically significant.</p>", "links"=>[], "tags"=>["skf-96365", "homeostasis", "pc12"], "article_id"=>168287, "categories"=>["Biotechnology", "Biochemistry", "Neuroscience", "Pharmacology"], "users"=>["Tao Chen", "Jie Zhu", "Chi Zhang", "Kai Huo", "Zhou Fei", "Xiao-fan Jiang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055601.g003", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_SKF_96365_on_Ca_2_homeostasis_in_MPP_treated_PC12_cells_/168287", "title"=>"Effect of SKF-96365 on Ca<sup>2+</sup> homeostasis in MPP<sup>+</sup>-treated PC12 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:10:38"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

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