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
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping