PUBLICATION
Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish
- Authors
- Félix, L.M., Serafim, C., Valentim, A.M., Antunes, L.M., Matos, M., Coimbra, A.M.
- ID
- ZDB-PUB-170720-13
- Date
- 2017
- Source
- Toxicology letters 279: 1-8 (Journal)
- Registered Authors
- Keywords
- Ketamine, apoptosis, development, gene expression, proliferation, zebrafish
- MeSH Terms
-
- Anesthetics, Dissociative/toxicity*
- Animals
- Apoptosis/drug effects*
- Apoptosis/genetics
- Apoptosis Regulatory Proteins/genetics*
- Apoptosis Regulatory Proteins/metabolism
- Blastula/drug effects*
- Blastula/metabolism
- Blastula/pathology
- Cell Proliferation/drug effects
- Dose-Response Relationship, Drug
- Gene Expression Regulation, Developmental/drug effects*
- Ketamine/toxicity*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Risk Assessment
- Teratogens/toxicity*
- Time Factors
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 28716577 Full text @ Toxicol. Lett.
- CTD
- 28716577
Citation
Félix, L.M., Serafim, C., Valentim, A.M., Antunes, L.M., Matos, M., Coimbra, A.M. (2017) Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish. Toxicology letters. 279:1-8.
Abstract
Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages). Exposure at the 256-cell stage to ketamine induced an up-regulation of casp8 and pcna at 8 hpf while changes in pcna at the mRNA level were observed at 24 hpf. After the 50% epiboly stage exposure, the mRNA levels of casp9 were increased at 8 and 24 hpf while aifm1 was affected at 24 hpf. Both tp53 and pcna expressions were increased at 8 hpf. After exposure during the 1-4 somites stage, no meaningful changes on transcript levels were observed. The distribution of apoptotic cells and the caspase-like enzymatic activities of caspase-3 and -9 were not affected by ketamine exposure. It is proposed that ketamine exposure at the 256-cell stage induced a cooperative mechanism between proliferation and cellular death while following exposure at the 50% epiboly, a p53-dependent and -independent caspase activation may occur. Finally, at the 1-4 somites stage, the defence mechanisms are already fully in place to protect against ketamine-insult. Thus, ketamine teratogenicity seems to be dependent on the functional mechanisms present in each developmental stage.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping