ArticleThe Journal of pharmacology and experimental therapeutics2011
Impact of pyrrolidine dithiocarbamate and interleukin-6 on mammalian target of rapamycin complex 1 regulation and global protein translation.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome.NPJ aging and mechanisms of disease · 2020Article
- Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological.Molecules (Basel, Switzerland) · 2019Review
- Short-term pyrrolidine dithiocarbamate administration attenuates cachexia-induced alterations to muscle and liver in ApcMin/+ mice.Oncotarget · 2016Article
- The pathogenic role of persistent milk signaling in mTORC1- and milk-microRNA-driven type 2 diabetes mellitus.Current diabetes reviews · 2015Review
- MiR-630 inhibits proliferation by targeting CDC7 kinase, but maintains the apoptotic balance by targeting multiple modulators in human lung cancer A549 cells.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 4 countries.
Funding
Abstract
Interleukin-6 (IL-6) is a proinflammatory cytokine that exerts a wide range of cellular, physiological, and pathophysiological responses. Pyrrolidine dithiocarbamate (PDTC) antagonizes the cellular responsiveness to IL-6 through impairment in signal transducer and activator of transcription-3 activation and downstream signaling. To further elucidate the biological properties of PDTC, global gene expression profiling of human HepG2 hepatocellular carcinoma cells was carried out after treatment with PDTC or IL-6 for up to 8 h. Through an unbiased pathway analysis method, gene array analysis showed dramatic and temporal differences in expression changes in response to PDTC versus IL-6. A significant number of genes associated with metabolic pathways, inflammation, translation, and mitochondrial function were changed, with ribosomal protein genes and DNA damage-inducible transcript 4 protein (DDIT4) primarily up-regulated with PDTC but down-regulated with IL-6. Quantitative polymerase chain reaction and Western blot analyses validated the microarray data and showed the reciprocal expression pattern of the mammalian target of rapamycin (mTOR)-negative regulator DDIT4 in response to PDTC versus IL-6. Cell treatment with PDTC resulted in a rapid and sustained activation of Akt and subsequently blocked the IL-6-mediated increase in mTOR complex 1 function through up-regulation in DDIT4 expression. Conversely, down-regulation of DDIT4 with small interfering RNA dampened the capacity of PDTC to block IL-6-dependent mTOR activation. The overall protein biosynthetic capacity of the cells was severely blunted by IL-6 but increased in a rapamycin-independent pathway by PDTC. These results demonstrate a critical effect of PDTC on mTOR complex 1 function and provide evidence that PDTC can reverse IL-6-related signaling via induction of DDIT4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.