PUBLICATION
Propofol impairs specification of retinal cell types in zebrafish by inhibiting Zisp-mediated Noggin-1 palmitoylation and trafficking
- Authors
- Fan, X., Yang, H., Hu, L., Wang, D., Wang, R., Hao, A., Chen, X.
- ID
- ZDB-PUB-210323-1
- Date
- 2021
- Source
- Stem Cell Research & Therapy 12: 195 (Journal)
- Registered Authors
- Keywords
- Noggin, Palmitoylation, Propofol, Retina, Zebrafish, Zisp
- MeSH Terms
-
- Animals
- Apoptosis
- In Situ Nick-End Labeling
- Lipoylation
- Neurons
- Propofol*/pharmacology
- Retina
- Zebrafish/genetics
- PubMed
- 33743805 Full text @ Stem Cell Res. Ther.
Citation
Fan, X., Yang, H., Hu, L., Wang, D., Wang, R., Hao, A., Chen, X. (2021) Propofol impairs specification of retinal cell types in zebrafish by inhibiting Zisp-mediated Noggin-1 palmitoylation and trafficking. Stem Cell Research & Therapy. 12:195.
Abstract
Background Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway.
Methods The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2'-deoxyuridine labeling, co-immunoprecipitation, and acyl-biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types.
Results Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate.
Conclusions Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping