PUBLICATION
Gamma-Aminobutyric Acid (GABA) Promotes Growth in Zebrafish Larvae by Inducing IGF-1 Expression via GABAA and GABAB Receptors
- Authors
- Athapaththu, A.M.G.K., Molagoda, I.M.N., Jayasooriya, R.G.P.T., Choi, Y.H., Jeon, Y.J., Park, J.H., Lee, B.J., Kim, G.Y.
- ID
- ZDB-PUB-211025-42
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(20): (Journal)
- Registered Authors
- Jeon, You-Jin
- Keywords
- GABA, GABA receptors, IGF-1, growth performance
- MeSH Terms
-
- Animals
- Cell Line
- Dose-Response Relationship, Drug
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/drug effects
- Glycerophosphates/pharmacology
- Larva/drug effects
- Larva/growth & development
- Larva/metabolism
- Mice
- Podophyllotoxin/analogs & derivatives
- Podophyllotoxin/pharmacology
- Receptor, IGF Type 1/metabolism
- Receptors, GABA/metabolism*
- Receptors, Somatotropin/metabolism
- Somatomedins/metabolism*
- Zebrafish/growth & development*
- Zebrafish/metabolism
- Zebrafish Proteins/metabolism*
- gamma-Aminobutyric Acid/pharmacology*
- PubMed
- 34681914 Full text @ Int. J. Mol. Sci.
Citation
Athapaththu, A.M.G.K., Molagoda, I.M.N., Jayasooriya, R.G.P.T., Choi, Y.H., Jeon, Y.J., Park, J.H., Lee, B.J., Kim, G.Y. (2021) Gamma-Aminobutyric Acid (GABA) Promotes Growth in Zebrafish Larvae by Inducing IGF-1 Expression via GABAA and GABAB Receptors. International Journal of Molecular Sciences. 22(20):.
Abstract
Insulin-like growth factor-1 (IGF-1) primarily increases the release of gamma-aminobutyric acid (GABA) in neurons; moreover, it is responsible for the promotion of longitudinal growth in children and adolescents. Therefore, in this study, we investigated whether exogenous GABA supplementation activates IGF-mediated growth performance. Zebrafish larvae treated with GABA at three days post fertilization (dpf) showed a significant increase in the total body length from 6 to 12 dpf through upregulation of growth-stimulating genes, including IGF-1, growth hormone-1 (GH-1), growth hormone receptor-1 (GHR-1), and cholecystokinin A (CCKA). In particular, at 9 dpf, GABA increased total body length from 3.60 ± 0.02 to 3.79 ± 0.03, 3.89 ± 0.02, and 3.92 ± 0.04 mm at concentrations of 6.25, 12.5, and 25 mM, and the effect of GABA at 25 mM was comparable to 4 mM β-glycerophosphate (GP)-treated larvae (3.98 ± 0.02 mm). Additionally, the highest concentration of GABA (50 mM) -induced death in 50% zebrafish larvae at 12 dpf. GABA also enhanced IGF-1 expression and secretion in preosteoblast MC3T3-E1 cells, concomitant with high levels of the IGF-1 receptor gene (IGF-1R). In zebrafish larvae, the GABA-induced growth rate was remarkably decreased in the presence of an IGF-1R inhibitor, picropodophyllin (PPP), which indicates that GABA-induced IGF-1 enhances growth rate via IGF-1R. Furthermore, we investigated the effect of GABA receptors on growth performance along with IGF-1 activation. Inhibitors of GABAA and GABAB receptors, namely bicuculline and CGP 46381, respectively, considerably inhibited GABA-induced growth rate in zebrafish larvae accompanied by a marked decrease in the expression of growth-stimulating genes, including IGF-1, GH-1, GHR-1, and CCKA, but not with an inhibitor of GABAC receptor, TPMPA. Additionally, IGF-1 and IGF-1R expression was impaired in bicuculline and CGP 46381-treated MC3T3-E1 cells, but not in the cells treated with TPMPA. Furthermore, treatment with bicuculline and CGP 46381 significantly downregulated GABA-induced IGF-1 release in MC3T3-E1 cells. These data indicate that GABA stimulates IGF-1 release via GABAA and GABAB receptors and leads to growth promotion performance via IGF-1R.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping