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Heme regulates exocrine peptidase precursor genes in zebrafish.
Exp Biol Med (Maywood). 2007 Oct; 232(9):1170-80.EB

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.

Authors+Show Affiliations

Department of Zoology and Stephenson Research & Technology Center, University of Oklahoma, Norman, Oklahoma 73019, USA. hwang@ou.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17895525

Citation

Wang, Han, et al. "Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish." Experimental Biology and Medicine (Maywood, N.J.), vol. 232, no. 9, 2007, pp. 1170-80.
Wang H, Zhou Q, Kesinger JW, et al. Heme regulates exocrine peptidase precursor genes in zebrafish. Exp Biol Med (Maywood). 2007;232(9):1170-80.
Wang, H., Zhou, Q., Kesinger, J. W., Norris, C., & Valdez, C. (2007). Heme regulates exocrine peptidase precursor genes in zebrafish. Experimental Biology and Medicine (Maywood, N.J.), 232(9), 1170-80.
Wang H, et al. Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish. Exp Biol Med (Maywood). 2007;232(9):1170-80. PubMed PMID: 17895525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heme regulates exocrine peptidase precursor genes in zebrafish. AU - Wang,Han, AU - Zhou,Qingchun, AU - Kesinger,Jason W, AU - Norris,Chad, AU - Valdez,Cammi, PY - 2007/9/27/pubmed PY - 2007/12/6/medline PY - 2007/9/27/entrez SP - 1170 EP - 80 JF - Experimental biology and medicine (Maywood, N.J.) JO - Exp Biol Med (Maywood) VL - 232 IS - 9 N2 - 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. SN - 1535-3702 UR - https://www.unboundmedicine.com/medline/citation/17895525/Heme_regulates_exocrine_peptidase_precursor_genes_in_zebrafish_ L2 - https://journals.sagepub.com/doi/10.3181/0703-RM-77?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -