PUBLICATION
The knockout of cytoglobin 1 in zebrafish (Danio rerio) alters lipid metabolism, iron homeostasis and oxidative stress response
- Authors
- Schlosser, A., Helfenrath, K., Wisniewsky, M., Hinrichs, K., Burmester, T., Fabrizius, A.
- ID
- ZDB-PUB-230810-43
- Date
- 2023
- Source
- Biochimica et biophysica acta. Molecular cell research 1870(8): 119558 (Journal)
- Registered Authors
- Fabrizius, Andrej
- Keywords
- CRISPR/Cas9, Cytoglobin 1, Inflammation, Lipid metabolism, ROS, Zebrafish
- MeSH Terms
-
- Lipids
- Cytoglobin/genetics
- Cytoglobin/metabolism
- Homeostasis/genetics
- Reactive Oxygen Species
- Mammals/metabolism
- Globins*/genetics
- Globins*/metabolism
- Lipid Metabolism/genetics
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Oxidative Stress/genetics
- Mice
- Male
- Animals
- PubMed
- 37549740 Full text @ BBA Molecular Cell Research
Citation
Schlosser, A., Helfenrath, K., Wisniewsky, M., Hinrichs, K., Burmester, T., Fabrizius, A. (2023) The knockout of cytoglobin 1 in zebrafish (Danio rerio) alters lipid metabolism, iron homeostasis and oxidative stress response. Biochimica et biophysica acta. Molecular cell research. 1870(8):119558.
Abstract
Cytoglobin (Cygb) is an evolutionary ancient heme protein with yet unclear physiological function(s). Mammalian Cygb is ubiquitously expressed in all tissues and is proposed to be involved in reactive oxygen species (ROS) detoxification, nitric oxide (NO) metabolism and lipid-based signaling processes. Loss-of-function studies in mouse associate Cygb with apoptosis, inflammation, fibrosis, cardiovascular dysfunction or oncogenesis. In zebrafish (Danio rerio), two cygb genes exist, cytoglobin 1 (cygb1) and cytoglobin 2 (cygb2). Both have different coordination states and distinct expression sites within zebrafish tissues. The biological roles of the cygb paralogs are largely uncharacterized. We used a CRISPR/Cas9 genome editing approach and generated a knockout of the penta-coordinated cygb1 for in vivo analysis. Adult male cygb1 knockouts develop phenotypic abnormalities, including weight loss. To identify the molecular mechanisms underlying the occurrence of these phenotypes and differentiate between function and effect of the knockout we compared the transcriptomes of cygb1 knockout at different ages to age-matched wild-type zebrafish. We found that immune regulatory and cell cycle regulatory transcripts (e.g. tp53) were up-regulated in the cygb1 knockout liver. Additionally, the expression of transcripts involved in lipid metabolism and transport, the antioxidative defense and iron homeostasis was affected in the cygb1 knockout. Cygb1 may function as an anti-inflammatory and cytoprotective factor in zebrafish liver, and may be involved in lipid-, iron-, and ROS-dependent signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping