Back to Search
Start Over
Cucurbitacin B induces neurogenesis in PC12 cells and protects memory in APP/PS1 mice
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2019
- Publisher :
- John Wiley and Sons Inc., 2019.
-
Abstract
- Cucurbitacin B (CuB) isolated from Cucumis melo by using a PC12 cell bioassay system exhibited significant nerve growth factor (NGF)‐mimic or NGF‐enhancing activity in PC12 and primary neuron cells. It was also demonstrated pro‐neurogenesis effects in ICR and APP/PS1 mice and improved memory deficit of APP/PS1 mice. Its possible mechanism includes significant induction of the phosphorylation of glucocorticoid receptor (GR), protein kinase C (PKC), phospholipase C (PLC) and inhibition of cofilin. ChemProteoBase profiling, binding assay and cellular thermal shift assay (CETSA) were used to determine the target protein. Results revealed that CuB could affect actin dynamics as an actin inhibitor but did not bind with GR. The protein level of cofilin in PC12 cells after treating 0.3 μM and different temperatures was significantly higher than that of control group. Other neurotrophic signalling pathways, such as TrkA/TrkB, were analysed with specific inhibitors and Western blot. The inhibitors of TrkA, PLC, PKC, Ras, Raf and ERK1/2 significantly decreased the percentage of PC12 cells with neurite outgrowth and shortened the length of neurite outgrowth induced by CuB. CuB significantly induced the phosphorylation of TrkA, ERK and CREB. The phosphorylation of these proteins was obviously decreased by their specific inhibitors. These results suggest that cofilin is a candidate target protein of CuB in PC12 cells and that the GR/PLC/PKC and TrkA/Ras/Raf/ERK signalling pathways play important roles in the neuroprotective effect of CuB.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
cucurbitacin B
Neurite
Neurogenesis
Neuronal Outgrowth
Tropomyosin receptor kinase B
cofilin
CREB
PC12 Cells
03 medical and health sciences
Amyloid beta-Protein Precursor
Mice
0302 clinical medicine
Memory
Cell Line, Tumor
glucocorticoid receptor
Neurites
Animals
Protein kinase C
Neurons
Mice, Inbred ICR
Phospholipase C
biology
Chemistry
TrkA
Cell Biology
Original Articles
Cofilin
Alzheimer's disease
Triterpenes
Cell biology
Rats
030104 developmental biology
Nerve growth factor
Neuroprotective Agents
nervous system
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Original Article
Oligopeptides
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15824934 and 15821838
- Volume :
- 23
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....5a048d02402ce7d6ed978e779cdd67d1