Celastrol Stimulates Hypoxia-Inducible Factor-1 Activity in Tumor Cells by Initiating the ROS/Akt/p70S6K Signaling Pathway and Enhancing Hypoxia-Inducible Factor-1α Protein Synthesis
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{"title"=>"Celastrol stimulates hypoxia-inducible factor-1 activity in tumor cells by initiating the ros/akt/p70s6k signaling pathway and enhancing hypoxia-inducible factor-1α protein synthesis", "type"=>"journal", "authors"=>[{"first_name"=>"Xiaoxi", "last_name"=>"Han", "scopus_author_id"=>"55451019600"}, {"first_name"=>"Shengkun", "last_name"=>"Sun", "scopus_author_id"=>"7404509476"}, {"first_name"=>"Ming", "last_name"=>"Zhao", "scopus_author_id"=>"55735935800"}, {"first_name"=>"Xiang", "last_name"=>"Cheng", "scopus_author_id"=>"39761380700"}, {"first_name"=>"Guozhu", "last_name"=>"Chen", "scopus_author_id"=>"55733489300"}, {"first_name"=>"Song", "last_name"=>"Lin", "scopus_author_id"=>"55736629800"}, {"first_name"=>"Yifu", "last_name"=>"Guan", "scopus_author_id"=>"23004148900"}, {"first_name"=>"Xiaodan", "last_name"=>"Yu", "scopus_author_id"=>"57193744660"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "doi"=>"10.1371/journal.pone.0112470", "pui"=>"600460981", "sgr"=>"84911420350", "pmid"=>"25383959", "scopus"=>"2-s2.0-84911420350"}, "id"=>"3b0ce5fe-3aba-395c-b006-9de23eaf46a6", "abstract"=>"Celastrol, a tripterine derived from the traditional Chinese medicine plant Tripterygium wilfordii Hook F. (\"Thunder of God Vine\"), has been reported to have multiple effects, such as anti-inflammation, suppression of tumor angiogenesis, inhibition of tumor growth, induction of apoptosis and protection of cells against human neurodegenerative diseases. However, the mechanisms that underlie these functions are not well defined. In this study, we reported for the first time that Celastrol could induce HIF-1α protein accumulation in multiple cancer cell lines in an oxygen-independent manner and that the enhanced HIF-1α protein entered the nucleus and promoted the transcription of the HIF-1 target genes VEGF and Glut-1. Celastrol did not influence HIF-1α transcription. Instead, Celastrol induced the accumulation of the HIF-1α protein by inducing ROS and activating Akt/p70S6K signaling to promote HIF-1α translation. In addition, we found that the activation of Akt by Celastrol was transient. With increased exposure time, inhibition of Hsp90 chaperone function by Celastrol led to the subsequent depletion of the Akt protein and thus to the suppression of Akt activity. Moreover, in HepG2 cells, the accumulation of HIF-1α increased the expression of BNIP3, which induced autophagy. However, HIF-1α and BNIP3 did not influence the cytotoxicity of Celastrol because the main mechanism by which Celastrol kills cancer cells is through stimulating ROS-mediated JNK activation and inducing apoptosis. Furthermore, our data showed that the dose required for Celastrol to induce HIF-1α protein accumulation and enhance HIF-1α transcriptional activation was below its cytotoxic threshold. A cytotoxic dose of Celastrol for cancer cells did not display cytotoxicity in LO2 normal human liver cells, which indicated that the novel functions of Celastrol in regulating HIF-1 signaling and inducing autophagy might be used in new applications, such as in anti-inflammation and protection of cells against human neurodegenerative diseases. Future studies regarding these applications are required.", "link"=>"http://www.mendeley.com/research/celastrol-stimulates-hypoxiainducible-factor1-activity-tumor-cells-initiating-rosaktp70s6k-signaling", "reader_count"=>10, "reader_count_by_academic_status"=>{"Student > Ph. D. Student"=>2, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Student > Ph. D. Student"=>2, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>3, "Chemistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1786210"], "description"=>"<p>4a. Celastrol time-dependently enhanced the expression of HIF-1α and BNIP3. HepG2 cells were treated with 4 µM Celastrol in normoxia or hypoxia for the indicated times. The protein levels were determined by western blot analysis. 4b. Celastrol enhances LC3-II expression and the formation of LC-3 aggregates. HepG2 cells were treated with 4 µM Celastrol under normoxia or hypoxia for the indicated times. The LC3I/II protein levels were determined by western blot analysis (upper), and the LC3 aggregates were stained by indirect immunofluorescence and observed by confocal microscopy. 4c. Celastrol induced autophagy. HepG2 cells were transiently transfected with GFP-LC3, and 24 h later, the cells were treated with 4 µM Celastrol for another 24 h. GFP fluorescence was then observed by confocal microscopy.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234636, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_mediated_HIF_1_945_accumulation_stimulates_BNIP3_expression_and_induces_mitochondrial_autophagy_/1234636", "title"=>"Celastrol-mediated HIF-1α accumulation stimulates BNIP3 expression and induces mitochondrial autophagy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786206"], "description"=>"<p>1a. Celastrol dose-dependently enhanced HIF-1α expression under hypoxia. HepG2 cells were cultured in either normoxia or 3% hypoxia and treated with the indicated doses of Celastrol for 6 h. Western blotting was used to detect the expression of HIF-1α and HIF-1β, and β-actin was used as a loading control; an arrow shows the position of HIF-1α. The histogram results are representative of the mean ± SD of three independent experiments. 1b. Celastrol time-dependently enhanced HIF-1α expression under hypoxia. HepG2 cells were cultured with 4 µM Celastrol for the indicated time in hypoxia. 1c. Celastrol enhanced HIF-1α expression in HepG2 cells under mimetic hypoxia induced by 100 µM CoCl<sub>2</sub> and treated for 6 h. 1d. Celastrol dose-dependently enhanced HIF-1α expression under normoxia. HepG2 cells were treated with the indicated doses of Celastrol under normoxia for 6 h, and 100 µg of total protein was used for western blotting to detect HIF-1 proteins with a long exposure. 1e. Celastrol enhanced HIF-1α expression in multiple cell lines. MCF-7, HeLa, PC-3 and H1299 cells were treated with the indicated doses of Celastrol for 12 h under 3% hypoxia, and western blotting was used to detect the HIF-1 proteins. 1f. Celastrol decreased the levels of other Hsp90 client proteins but increased that of HIF-1α. HepG2 cells were treated with normal medium, 4 µM Celastrol for 6 h, 5 µM MG132 for 6 h or pretreated with MG132 for 1 h then treated with Celastrol for 6 h. Protein expression was determined by western blotting with the corresponding antibodies.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234632, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g001", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_increases_the_protein_level_of_HIF_1_945_/1234632", "title"=>"Celastrol increases the protein level of HIF-1α.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786215"], "description"=>"<p>8a. Low dose of Celastrol stimulated HIF-1α accumulation. HepG2 cells were treated with 0.5–1 µM Celastrol for 24 h in normoxia and hypoxia, and the viability of the cells was then detected by the MTT assay. 8b. 0.5–1 µM Celastrol did not arrest the cell cycle. HepG2 cells were treated with 0.5–1 µM Celastrol for 12 h in normoxia, and cell cycle analysis was performed using PI staining and flow cytometry. 8c. The effects of a low dose of Celastrol on HIF-1α protein expression and its transcriptional activation activity. HepG2 cells were treated with 0.5–1 µM Celastrol for 12 h in normoxia, and protein expression was determined using western blotting (upper). The transcriptional activation activity of HIF-1 was determined by transient transfection of HepG2 cells with HRE-luciferase reporter plasmids for 24 h followed by Celastrol exposure under normoxia for another 12 h. Then, HRE activity was analyzed using the luciferase assay (lower). The values are presented as the means ± SD of three independent experiments. 8d. The effect of Celastrol on LO2 normal liver cells. LO2 cells and HepG2 cells were treated with 4 µM Celastrol for 24–48 h, and the cytotoxicity of Celastrol was observed by microscopy (200×). Cell death and the cell cycle progression of the LO2 cells were measured by flow cytometry.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234641, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g008", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_could_stimulate_HIF_1_945_accumulation_with_a_dose_below_its_cytotoxic_threshold_/1234641", "title"=>"Celastrol could stimulate HIF-1α accumulation with a dose below its cytotoxic threshold.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786213"], "description"=>"<p>6a. Celastrol transiently activates p53 under normoxia but persistently activates p53 under hypoxia. HepG2 cells were cultured in normoxia or hypoxia with or without 4 µM Celastrol for the indicated times. The proteins were detected by western blotting. 6b. The effect of HIF1α knockdown on p53 expression under hypoxia. HepG2 cells were transfected with control or HIF1α siRNA for 24 h and then treated with or without 4 µM Celastrol under hypoxia for 24 h. The proteins were detected by western blotting. 6c. The effect of HIF1α knockdown on Celastrol-induced p53 expression and Akt and JNK activation under normoxia. HepG2 cells were transfected with control or HIF1α siRNA for 24 h and then treated with or without 4 µM Celastrol under normoxia for 24 h. The proteins were detected by western blotting. 6d, 6e. Suppression of ROS-induced JNK activity could prevent Celastrol-mediated cell death. HepG2 cells were pretreated with either the ROS scavenger 5 mM NAC or the JNK kinase inhibitor 40 µM SP600125 for 1 h and then treated with or without 4 µM Celastrol under normoxia for 24 h. Cell death was examined by microscopy (200×), as based on morphological changes, and quantified using the MTT assay. The proteins were detected by western blotting.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234639, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g006", "stats"=>{"downloads"=>1, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_kills_HepG2_cells_via_ROS_mediated_JNK_activation_/1234639", "title"=>"Celastrol kills HepG2 cells via ROS-mediated JNK activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786214"], "description"=>"<p>7a. Celastrol enhances HIF-1α expression and induces Akt activation in H1299 cells. H1299 cells were treated with the indicated doses of Celastrol for 6 h, and the proteins were detected by western blotting. 7b. Celastrol time-dependently induces ROS accumulation in H1299 cells. H1299 cells were treated with 4 µM Celastrol for the indicated times. The levels of ROS were measured by DCFH-DA staining and subsequently assayed by flow cytometry. 7c. Suppression of ROS-induced JNK activity could prevent Celastrol-mediated H1299 cell death. H1299 cells were pretreated with either the ROS scavenger 5 mM NAC or the JNK kinase inhibitor 40 µM SP600125 for 1 h and then treated with or without 4 µM Celastrol under normoxia for 24 h. Cell death was examined by microscopy (200×) and measured by Annexin-V/PI staining and flow cytometry. The proteins were detected by western blotting.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234640, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g007", "stats"=>{"downloads"=>5, "page_views"=>72, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_kills_p53_null_H1299_cells_via_ROS_mediated_JNK_activation_/1234640", "title"=>"Celastrol kills p53-null H1299 cells via ROS-mediated JNK activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786212"], "description"=>"<p>5a. Celastrol enhanced the HIF-1α and BNIP3 expression that was accompanied by increased PARP cleavage under hypoxia. HepG2 cells were cultured under normoxia or hypoxia with or without 4 µM Celastrol for 24 h. Western blotting was used to detect protein expression. 5b. The cytotoxicity of Celastrol was enhanced under hypoxia. HepG2 cells were cultured under normoxia or hypoxia with or without 2–4 µM Celastrol for 24 h. The cells were then stained with Annexin-V/PI and analyzed by flow cytometry. The data are presented as the mean values obtained from three independent experiments. 5c. Z-VAD blocked Celastrol-induced PARP cleavage but did not affect HIF-1α accumulation. HepG2 cells were pre-treated with 10 µM zVAD for 1 h then exposed to 4 µM Celastrol for another 6 h. The proteins were detected by western blot analysis. 5d. Knockdown of HIF-1α did not affect Celastrol-induced PARP cleavage. HepG2 cells were transfected with a non-silencing siRNA or HIF-1α siRNA for 24 h, and the cells were then treated with 4 µM Celastrol for 24 h. The proteins were detected by western blot analysis. 5e, 5f. Knockdown of BNIP3 did not affect Celastrol-induced cell death. HepG2 cells were transfected with non-silencing siRNA or BNIP3 siRNA for 24 h, and the cells were then treated with 4 µM Celastrol for 24 h. Cell death was measured by Annexin-V/PI staining and flow cytometry, and the proteins were detected by western blotting.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234638, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g005", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Knockdown_of_HIF_1_945_or_BNIP3_did_not_influence_Celastrol_induced_cell_apoptosis_under_hypoxia_/1234638", "title"=>"Knockdown of HIF-1α or BNIP3 did not influence Celastrol-induced cell apoptosis under hypoxia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786209"], "description"=>"<p>3a. Celastrol enhances HIF-1α protein expression, which was localized in the nucleus. HepG2 cells were cultured in medium with or without 4 µM Celastrol for 6 h under normoxia or hypoxia. The subcellular localization of HIF-1α was determined by immunofluorescent staining using the anti-HIF-1α antibody,and the nucleus was immunolabeled with Hoechst 33258. 3b. HepG2 cells were treated with the indicated dose of Celastrol for 6 h, protein was extracted from the nucleus and cytosol, and the protein expression levels were revealed by western blot analysis. PARP served as the nuclear protein loading control. 3c. Celastrol promotes HIF-1α transcriptional activation activity. After transient transfection with the HRE-luciferase reporter plasmids for 24 h, HepG2 cells were challenged with the indicated doses of Celastrol in normoxia or hypoxia for another 6 h. Then, the HIF-1α transcriptional activation activity was analyzed by luciferase assay. The values are presented as the means ± SD of three independent experiments. 3d. Celastrol promotes the transcription of the HIF-1α target genes VEGF and Glut-1. The VEGF and Glut-1 mRNA levels were evaluated by real-time PCR. The values are presented as the means±SD of three independent experiments.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234635, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_promotes_the_hypoxia_induced_accumulation_of_the_HIF_1_945_protein_in_the_nucleus_which_increases_the_transcriptional_activity_of_HIF_1_945_target_genes_/1234635", "title"=>"Celastrol promotes the hypoxia-induced accumulation of the HIF-1α protein in the nucleus, which increases the transcriptional activity of HIF-1α target genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786208"], "description"=>"<p>2a. Celastrol did not affect HIF-1α transcription. After treatment with different concentrations of Celastrol for 6 h, total RNA was extracted, and the mRNA levels of HIF-1α and RPL13A were determined by RT-PCR. The relative expression of HIF-1α was normalized to that of RPL13A. The values are presented as the means ± SD of three independent experiments. 2b. Celastrol enhanced the expression of the HIF-1α P402A/P564A mutant. HeLa cells were seeded in 6-well plates and transiently transfected with either pcDNA-V5 empty vector (ctrl) or pcDNA3-P402A/P564A-HIF-1α-V5 (mtHIF-1). Twenty-four hours later, the cells were treated with 1–2 µM Celastrol for 6 h under normoxia. Mutant HIF-1α expression was analyzed by western blotting with the anti-V5 antibody. 2c. Celastrol did not affect HIF-1α ubiquitination. HepG2 cells were treated separately with 4 µM Celastrol, 10 µM MG132 or Celastrol plus MG132 for 4 h under normoxia, and the ub-HIF-1α protein level was determined by western blotting using the anti-HIF-1α antibody. 2d. The effect of the protein synthesis inhibitor CHX on Celastrol-induced HIF-1α accumulation. HepG2 cells were treated with or without 4 µM Celastrol for 6 h. Then, 10 µM CHX was added to the culture medium, and the cells were collected at the indicated times (left). HepG2 cells were cultured in medium containing 100 µM CoCl<sub>2</sub> with or without 4 µM Celastrol for 4 h, then 10 µM CHX was added, and the cells were collected at the indicated times (right). The HIF-1α protein level was analyzed by western blot analysis. 2e. Celastrol induced AKT/p70S6K activation under normoxia and hypoxia. HepG2 cells were challenged with the indicated doses of Celastrol for 6 h under normoxia or hypoxia. The protein levels were analyzed by western blotting with the corresponding antibodies. 2f. Celastrol induced AKT/p70S6K activation under serum starvation. HepG2 cells were cultured in serum-free medium for 24 h. Then, 10% FBS, 4 µM Celastrol or both were added, and the cells were cultured for another 6 h. The protein expression was analyzed by western blotting with the corresponding antibodies. 2 g. Celastrol induced the accumulation of ROS. HepG2 cells were treated with 4 µM Celastrol for 12 h under normoxia. The levels of ROS were measured by DCFH-DA staining and subsequently assayed by flow cytometry. 2 h. The effect of Celastrol-induced HIF-1α accumulation depends on ROS-mediated AKT activation. HepG2 cells were pretreated with 5 mM NAC or 10 µM LY294002 for 1 h. Then, 4 µM Celastrol was added to the culture medium, and the cells were cultured for another 6 h. The protein expression was determined by western blotting with the corresponding antibodies.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234634, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_increases_the_HIF_1_945_protein_level_by_enhancing_its_translation_/1234634", "title"=>"Celastrol increases the HIF-1α protein level by enhancing its translation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1786217"], "description"=>"<p>In our system, we showed that Celastrol could induce ROS-mediated autophagy and apoptosis. Celastrol-induced autophagy occurred at an early phase and was initiated by ROS to stimulate AKT/p70S6K signal activation, which promotes HIF-1α translation and BNIP3 expression, leading to autophagy. Apoptosis occurred at a late phase, and the main mechanism by which Celastrol killed HepG2 and H1299 cells was through the ROS-mediated activation of JNK and inhibition of Hsp90 chaperone function, which led to Akt protein depletion and a decrease in Akt activity, finally resulting in the induction of apoptosis.</p>", "links"=>[], "tags"=>["jnk", "cancer cells", "target genes VEGF", "ros", "Neurodegenerative diseases", "HepG 2 cells", "BNIP", "Hsp 90 chaperone function", "cancer cell lines", "protein", "Chinese medicine plant Tripterygium wilfordii Hook F", "hif", "lo", "celastrol"], "article_id"=>1234643, "categories"=>["Uncategorised"], "users"=>["Xiaoxi Han", "Shengkun Sun", "Ming Zhao", "Xiang Cheng", "Guozhu Chen", "Song Lin", "Yifu Guan", "XiaoDan Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112470.g009", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_mechanism_by_which_Celastrol_induces_autophagy_and_apoptosis_/1234643", "title"=>"The mechanism by which Celastrol induces autophagy and apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-10 03:21:27"}

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Relative Metric

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