| Description: |
Cytosporone B is a naturally occurring agonist for Nur77, it also is a Salmonella pathogenicity island 1 (SPI-1)-inhibitor, it may have potential in drug development against antibiotic-resistant Salmonella. Cytosporone B can elevate blood glucose levels in fasting C57 mice, an effect that is accompanied by induction of multiple genes involved in gluconeogenesis. Cytosporone B can inhibit transforming growth factor-b (TGF-β)-induced contraction of human corneal fibroblasts (HCFs), likely as a result of its attenuation of the up-regulation of α-SMA expression. |
| Targets: |
TGF-β/Smad | Antifection | Nur77 | α-SMA | SPI-1 |
| In vitro: |
| Antimicrobial Agents & Chemotherapy, 2013 , 57 (5) :2191-8. | | Cytosporone B, an Inhibitor of the Type III Secretion System of Salmonella enterica Serovar Typhimurium[Reference: WebLink] |
METHODS AND RESULTS:
In this study, we identified several analogs of Cytosporone B (Csn-B) that strongly block the secretion of Salmonella pathogenicity island 1 (SPI-1)-associated effector proteins, without affecting the secretion of flagellar protein FliC in vitro. Csn-B and two other derivatives exhibited a strong inhibitory effect on SPI-1-mediated invasion to HeLa cells, while no significant toxicity to bacteria was observed. Nucleoid proteins Hha and H-NS bind to the promoters of SPI-1 regulator genes hilD, hilC, and rtsA to repress their expression and consequently regulate the expression of SPI-1 apparatus and effector genes. We found that Csn-B upregulated the transcription of hha and hns, implying that Csn-B probably affected the secretion of effectors through the Hha–H-NS regulatory pathway.
CONCLUSIONS:
In summary, this study presented an effective SPI-1 inhibitor, Csn-B, which may have potential in drug development against antibiotic-resistant Salmonella. |
|
| In vivo: |
| Nat Chem Biol. 2008 Sep;4(9):548-56. | | Cytosporone B is an agonist for nuclear orphan receptor Nur77.[Pubmed: 18690216 ] | Nuclear orphan receptor Nur77 has important roles in many biological processes. However, a physiological ligand for Nur77 has not been identified.
METHODS AND RESULTS:
Here, we report that the octaketide Cytosporone B (Csn-B) is a naturally occurring agonist for Nur77. Csn-B specifically binds to the ligand-binding domain of Nur77 and stimulates Nur77-dependent transactivational activity towards target genes including Nr4a1 (Nur77) itself, which contains multiple consensus response elements allowing positive autoregulation in a Csn-B-dependent manner. Csn-B also elevates blood glucose levels in fasting C57 mice, an effect that is accompanied by induction of multiple genes involved in gluconeogenesis. These biological effects were not observed in Nur77-null (Nr4a1-/-) mice, which indicates that Csn-B regulates gluconeogenesis through Nur77. Moreover, Csn-B induced apoptosis and retarded xenograft tumor growth by inducing Nur77 expression, translocating Nur77 to mitochondria to cause cytochrome c release.
CONCLUSIONS:
Thus, Csn-B may represent a promising therapeutic drug for cancers and hypoglycemia, and it may also be useful as a reagent to increase understanding of Nur77 biological function. |
|
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)