dc.contributor.author | Han Wang | |
dc.contributor.author | Qingchun Zhou | |
dc.contributor.author | Jason W. Kesinger | |
dc.contributor.author | Chad Norris | |
dc.contributor.author | Cammi Valdez | |
dc.date.accessioned | 2016-01-14T19:54:01Z | |
dc.date.accessioned | 2016-03-30T15:32:23Z | |
dc.date.available | 2016-01-14T19:54:01Z | |
dc.date.available | 2016-03-30T15:32:23Z | |
dc.date.issued | 2007-10-01 | |
dc.identifier.citation | Wang, H., Zhou, Q., Kesinger, J. W., Norris, C., & Valdez, C. (2007). Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish. Experimental Biology and Medicine, 232(9), 1170-1180. doi: 10.3181/0703-rm-77 | en_US |
dc.identifier.uri | https://hdl.handle.net/11244/25577 | |
dc.description.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 (yqetp61) 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 (sautb223) larvae, carrying a mutation in the gene encoding δ-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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Experimental Biology and Medicine | |
dc.subject | heme | en_US |
dc.subject | zymogens | en_US |
dc.subject | pancreas | en_US |
dc.subject | porphyria | en_US |
dc.subject | zebrafish | en_US |
dc.title | Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish | en_US |
dc.type | Research Article | en_US |
dc.description.peerreview | Yes | en_US |
dc.description.peerreviewnotes | https://us.sagepub.com/en-us/nam/manuscript-submission-guidelines | en_US |
dc.identifier.doi | 10.3181/0703-rm-77 | en_US |
dc.rights.requestable | false | en_US |