Euphohelioscopin A Is a PKC Activator Capable of Inducing Macrophage Differentiation

Lichtervelde, Lorenzo de; Antal, Corina E.; Boitano, Anthony E.; Wang, Ying; Krastel, Philipp; Petersen, Frank; Newton, Alexandra C.; Cooke, M.; Schultz, Peter G.

doi:10.1016/j.chembiol.2012.06.010

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…Female Balb/c mice (Henan animal research center), 6-8 weeks of age, were used in all animal experiments of this study (de Lichtervelde et al . 2012; Zhang et al .…”

Section: Methodsmentioning

confidence: 99%

Characterization of Isoforms of the Ovine Granulocyte Colony Stimulating Factor

Zhao

Chen

Zhang

et al. 2019

Preprint

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The granulocyte colony-stimulating factor (GCSF) regulates the 28 maturation, proliferation, and differentiation of precursor cells of neutrophilic 29 granulocytes, and has been widely studied in several species. To investigate the 30 function of variants of sheep GCSF (sGCSF), this study compared difference in their 31 mRNA expression levels. Both the activity and mRNA expression level of GCSFv2 32 were higher than those of GCSFv1. Their sequences were aligned, which showed that 33 they had the highest homology with bovine GCSF. Then, predicted ovine GCSF 34 isoforms and their constant C-terminals were cloned and expressed, which were stably 35 expressed in mammalian cells. After purification, all GCSF functions were different 36 both in vitro and in vivo, and the GCSF C-terminal was best. These results indicated 37 that the ability to stimulate both the proliferation and differentiation of progenitor 38 cells and to activate the maturation of neutrophils could be used for research of 39 efficacious non-antibiotic protein drugs. Furthermore, GCSF can be used as candidate 40 target of genetic breeding to specifically improve sheep immunity. 41 42 45 neutrophilic granulocytes (Nickerson 1991). The GCSF coding gene is localized on 46 chromosome 11. The GCSF is a member of the long-chain subtype of the class 1 47 cytokine superfamily, which includes growth hormone, erythropoietin, interleukin 6, 48 and oncostatin M. The crystal structure of the GCSF is complexed to the BN-BC 49 4domains, which is the principal ligand-binding region of the GCSF receptor (GCSFR), 50 and forms a complex at a 2:2 ratio with the ligand. This complex has a non-51

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“…Female Balb/c mice (Henan animal research center), 6-8 weeks of age, were used in all animal experiments of this study (de Lichtervelde et al . 2012; Zhang et al .…”

Section: Methodsmentioning

confidence: 99%

Characterization of Isoforms of the Ovine Granulocyte Colony Stimulating Factor

Zhao

Chen

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…Euphohelioscopin A, a potent hit of a hematopoietic stem cell differentiation screen was subsequently identified to act on the protein kinase C (PKC) and exert its pro-monocytic effect by PKC activation (see Fig. 5) [11]. Due to the tumorigenic potential of PKC the scope of therapeutic applications for euphohelioscopin A remains to be defined.…”

Section: Cellular Processesmentioning

confidence: 98%

Natural products as probes in pharmaceutical research

Schmitt

Hoepfner

Krastel

2016

Journal of Industrial Microbiology and Biotechnology

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From the start of the pharmaceutical research natural products played a key role in drug discovery and development. Over time many discoveries of fundamental new biology were triggered by the unique biological activity of natural products. Unprecedented chemical structures, novel chemotypes, often pave the way to investigate new biology and to explore new pathways and targets. This review summarizes the recent results in the area with a focus on research done in the laboratories of Novartis Institutes for BioMedical Research. We aim to put the technological advances in target identification techniques in the context to the current revival of phenotypic screening and the increasingly complex biological questions related to drug discovery.

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“…The plant derived natural product euphohelioscopin A (Figure 14) 131 was identified through a screen using human CD34+ cells monitoring for the ability of compounds to promote differentiation to the granulocyte/monocytic (GM) lineage. 132 The natural product was found to decrease the percentage of CD34+ cells from 29% in control to 13% while increasing the number of total nucleated cells 2-fold. The cell surface marker CD45ra+ was increased to 79% versus controls possessing 50%.…”

Section: Euphohelioscopin Amentioning

confidence: 99%

Directing Stem Cell Fate: The Synthetic Natural Product Connection

Johnson

Siegel

2017

Chem. Rev.

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Stem cells possess remarkable potential for the treatment of a broad array of diseases including many that lack therapeutic options. However, the use of cell-based products derived from stem cells as therapeutics has limitations including rejection, sufficient availability, and lack of appropriate engraftment. Chemical control of stem cells provides potential solutions for overcoming many of the current limitations in cell-based therapeutics. The development of exogenous molecules to control stem cell self-renewal or differentiation has arrived at natural product-based agents as an important class of modulators. The ex vivo production of cryopreserved cellular products for use in tissue repair is a relatively new area of medicine in which the conventional hurdles to implementing chemicals to effect human health are changed. Translational challenges centered on chemistry, such as pharmacokinetics, are reduced. Importantly, in many cases the desired human tissues can be evaluated against new chemicals, and approaches to cellular regulation can be validated in the clinically applicable system. As a result linking new and existing laboratory syntheses of natural products with findings of the compounds' unique abilities to regulate stem cell fate provides opportunities for developing improved methods for tissue manufacture, accessing probe compounds, and generating new leads that yield manufactured cells with improved properties. This review provides a summary of natural products that have shown promise in controlling stem cell fate and which have also been fully synthesized thereby providing chemistry platforms for further development.

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Euphohelioscopin A Is a PKC Activator Capable of Inducing Macrophage Differentiation

Cited by 10 publications

References 28 publications

Characterization of Isoforms of the Ovine Granulocyte Colony Stimulating Factor

Characterization of Isoforms of the Ovine Granulocyte Colony Stimulating Factor

Natural products as probes in pharmaceutical research

Directing Stem Cell Fate: The Synthetic Natural Product Connection

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