Structure, mRNA expression and linkage mapping of the brain-type fatty acid-binding protein gene (fabp7) from zebrafish (Danio rerio)
EUROPEAN JOURNAL OF BIOCHEMISTRY
Authors: Liu, RZ; Denovan-Wright, EM; Wright, JM
Abstract
The brain fatty acid-binding protein (B-FABP) is involved in brain development and adult neurogenesis. We have determined the sequence of the gene encoding the B-FABP in zebrafish. The zebrafish B-FABP gene spans 2370 bp and contains four exons interrupted by three introns. The coding sequence of zebrafish B-FABP gene is identical to its cDNA sequence and the coding capacity of each exon is the same as that for the human and mouse B-FABP genes. A 1249 bp sequence 5' upstream of exon 1 of the zebrafish B-FABP gene was cloned and sequenced. Several brain development/growth-associated transcription factor binding elements, including POU-domain binding elements and the proposed lipogenic-associated transcription factor NF-Y elements, were found within the 5' region of the B-FABP gene. RT-PCR analysis using mRNA extracted from different tissues of adult zebrafish demonstrated that the zebrafish B-FABP mRNA was predominant in brain with lower levels in liver, testis and intestine, but not in ovary, skin, heart, kidney and muscle. Quantitative RT-PCR revealed a similar tissue-specific distribution for zebrafish B-FABP mRNA except that very low levels of B-FABP mRNA, normalized to beta-actin mRNA, were detected in the heart and muscle RNA, but not in liver RNA. Zebrafish B-FABP mRNA was detected by RT-PCR in embryos beyond 12 h postfertilization, suggesting a correlation of zebrafish B-FABP mRNA expression with early brain development. Radiation hybrid mapping assigned the zebrafish B-FABP gene to linkage group 17. Conserved syntenies of the zebrafish B-FABP gene and the human and mouse orthologous B-FABP genes were observed by comparative genomic analysis.
Tri-m-cresyl phosphate and PPAR/LXR interactions in seabream hepatocytes: revealed by computational modeling (docking) and transcriptional regulation of signaling pathways
TOXICOLOGY RESEARCH
Authors: Palermo, Francesco Alessandro; Cocci, Paolo; Mozzicafreddo, Matteo; Arukwe, Augustine; Angeletti, Mauro; Aretusi, Graziano; Mosconi, Gilberto
Abstract
The interactions between tri-m-cresyl phosphate (TMCP; an organophosphate flame retardant) and peroxisome proliferator activated receptors (PPARs) or liver X receptor alpha (LXR alpha) were investigated in seabream hepatocytes. The study was designed to characterize the binding of TMCP to PPAR alpha, PPAR. and LXR alpha by computational modeling (docking) and transcriptional regulation of signaling pathways. TMCP mainly established a non-polar interaction with each receptor. These findings reflect the hydrophobic nature of this binding site, with fish LXR alpha showing the highest binding efficiency. Further, we have investigated the ability of TMCP to activate PPAR and LXR controlled transcriptional processes involved in lipid/cholesterol metabolism. TMCP induced the expression of all the target genes measured. All target genes were up-regulated at all exposure doses, except for fatty acid binding protein 7 (FABP7) and carnitine palmitoyltransferase 1B. Collectively, our data indicate that TMCP can affect fatty acid synthesis/uptake and cholesterol metabolism through LXR alpha and PPARs, together with interactions between these transcription factors in seabream liver.