PUBLICATION
Heme regulates exocrine peptidase precursor genes in zebrafish
- Authors
- Wang, H., Zhou, Q., Kesinger, J.W., Norris, C., and Valdez, C.
- ID
- ZDB-PUB-071001-15
- Date
- 2007
- Source
- Experimental Biology and Medicine 232(9): 1170-1180 (Journal)
- Registered Authors
- Wang, Han
- Keywords
- heme, zymogens, pancreas, porphyria, zebrafish
- Datasets
- GEO:GSE8651
- MeSH Terms
-
- 5-Aminolevulinate Synthetase/genetics
- 5-Aminolevulinate Synthetase/metabolism
- Animals
- DNA Primers/metabolism
- Down-Regulation
- Embryo, Nonmammalian/enzymology
- Enzyme Precursors/genetics*
- Enzyme Precursors/metabolism
- Heme/deficiency
- Heme/metabolism*
- Hemin/metabolism
- Hemin/pharmacology
- Oligonucleotide Array Sequence Analysis
- Pancreas, Exocrine/enzymology*
- Pancreas, Exocrine/metabolism
- Peptide Hydrolases/genetics*
- Peptide Hydrolases/metabolism
- Phylogeny
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- PubMed
- 17895525 Full text @ Exp. Biol. Med.
Citation
Wang, H., Zhou, Q., Kesinger, J.W., Norris, C., and Valdez, C. (2007) Heme regulates exocrine peptidase precursor genes in zebrafish. Experimental Biology and Medicine. 232(9):1170-1180.
Abstract
We previously determined that yquem harbors a mutation in the gene encoding uroporphyrinogen decarboxylase (UROD), the fifth enzyme in heme biosynthesis, and established zebrafish yquem (yqe(tp61)) as a vertebrate model for human hepatoery-thropoietic porphyria (HEP). Here we report that six exocrine peptidase precursor genes, carboxypeptidase A, trypsin precursor, trypsin like, chymotrypsinogen B1, chymotrypsinogen 1-like, and elastase 2 like, are downregulated in yquem/urod (-/-), identified initially by microarray analysis of yquem/urod zebrafish and, subsequently, confirmed by in situ hybridization. We then determined downregulation of these six zymogens specifically in the exocrine pancreas of sauternes (sau(tb223)) larvae, carrying a mutation in the gene encoding delta-amino-levulinate synthase (ALAS2), the first enzyme in heme biosynthesis. We also found that ptf1a, a transcription factor regulating exocrine zymogens, is downregulated in both yquem/urod (-/-) and sau/alas2 (-/-) larvae. Further, hemin treatment rescues expression of ptf1a and these six zymogens in both yquem/urod (-/-) and sauternes/alas2 (-/-) larvae. Thus, it appears that heme deficiency downregulates ptf1a, which, in turn, leads to downregulation of exocrine zymogens. Our findings provide a better understanding of heme deficiency pathogenesis and enhance our ability to diagnose and treat patients with porphyria or pancreatic diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping