PUBLICATION
Modulation of peroxisome proliferator-activated receptors (PPARs) by PPARalpha- and PPARgamma-specific ligands and by 17beta-estradiol in isolated zebrafish hepatocytes
- Authors
- Ibabe, A., Herrero, A., and Cajaraville, M.P.
- ID
- ZDB-PUB-050623-4
- Date
- 2005
- Source
- Toxicology in vitro : an international journal published in association with BIBRA 19(6): 725-735 (Journal)
- Registered Authors
- Keywords
- Peroxisome proliferator-activated receptors (PPARs); Clofibrate; Hydroxyeicosatetraenoic acid (HETE); Prostaglandin J2 (PGJ2); 17?-estradiol; Zebrafish; Isolated hepatocytes; Immunohistochemistry
- MeSH Terms
-
- Animals
- Cell Nucleus/drug effects
- Cell Nucleus/metabolism
- Cell Proliferation/drug effects
- Cell Separation
- Cell Survival/drug effects
- Clofibrate/pharmacology
- Cytoplasm/drug effects
- Cytoplasm/metabolism
- Estradiol/pharmacology*
- Hepatocytes/drug effects*
- Hepatocytes/ultrastructure
- Hydroxyeicosatetraenoic Acids/pharmacology
- Hypolipidemic Agents/pharmacology
- Immunohistochemistry
- In Vitro Techniques
- Ligands
- PPAR alpha/drug effects*
- PPAR gamma/drug effects*
- Prostaglandin D2/analogs & derivatives
- Prostaglandin D2/pharmacology
- Zebrafish
- PubMed
- 15964169 Full text @ Toxicol. In Vitro
- CTD
- 15964169
Citation
Ibabe, A., Herrero, A., and Cajaraville, M.P. (2005) Modulation of peroxisome proliferator-activated receptors (PPARs) by PPARalpha- and PPARgamma-specific ligands and by 17beta-estradiol in isolated zebrafish hepatocytes. Toxicology in vitro : an international journal published in association with BIBRA. 19(6):725-735.
Abstract
Peroxisome proliferation is a phenomenon occurring when responsive animals are exposed to certain compounds so-called peroxisome proliferators and is regulated through a nuclear receptor named peroxisome proliferator-activated receptor (PPAR). PPAR family members exhibit a strong binding affinity for both saturated and unsaturated fatty acids. Activators of PPARalpha include a variety of endogenously present fatty acids, leukotrienes and hydroxyeicosatetraenoic acids (HETEs) and clinically used drugs, such as fibrates. PPARbeta activators include fatty acids, prostaglandin A(2) (PGA(2)) and prostacyclin (PGI(2)). PPARgamma is the most selective receptor and, among others, 15-deoxy-Delta(12,14) prostaglandin J(2) (PGJ(2)) has been described to be a PPARgamma-specific ligand. The aim of the present study was to determine if known PPARalpha and PPARgamma ligands were able to alter the expression of these subtypes in an in vitro model of zebrafish primary hepatocyte culture. With this purpose, a PPARalpha specific ligand (8S-HETE), a PPARgamma specific ligand (PGJ(2)) and a peroxisome proliferator of the fibrate class (clofibrate) were selected. In addition, the female hormone 17beta-estradiol was also used as it is known to interact with PPARs. After cell exposure for 24 h, cells were immunohistochemically stained for both PPARs and immunolabeling was quantified as percentage of positive nuclei and cells. Levels of expression of PPARs were also measured by image analysis as grey level per cell. Expression was induced for both PPARalpha and PPARgamma by clofibrate (at 0.5 mM for PPARalpha and at 1 and 2 mM for PPARgamma), by HETE (1 muM), and by PGJ(2) (0.3 and 1 muM for PPARalpha and 0.3 muM for PPARgamma). Expression of PPARgamma was also induced at 10 muM by 17beta-estradiol. The percentage of PPARalpha positive nuclei increased significantly at 1 muM HETE and the percentage of PPARgamma positive cells decreased at 10 muM 17beta-estradiol. As a conclusion, clofibrate, HETE and PGJ(2) are able to induce expression of both PPARalpha and PPARgamma in zebrafish primary hepatocyte cultures. Further studies are needed to identify how the expression of different PPAR subtypes is regulated and to elucidate the implication of PPAR subtypes in zebrafish cell functions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping