Leishmania spp. Delta-aminolevulinate-inducible neogenesis of porphyria by genetic complementation of incomplete heme biosynthesis pathway

Sujoy Dutta, Kazumichi Furuyama, Shigeru Sassa, Kwang Poo Chang

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

To further develop the Leishmania model for porphyria based on their deficiencies in heme biosynthesis, three Old World species were doubly transfected as before for Leishmania amazonensis with cDNAs, encoding the 2nd and 3rd enzymes in the pathway. Expression of the transgenes was verified immunologically at the protein level and functionally by uroporphyrin neogenesis that occurs only after exposure of the double-transfectants to delta-aminolevulinate. All species examined were equally deficient in heme biosynthesis, as indicated by the accumulation of uroporphyrin as the sole porphyrin and the production of coproporphyrin upon further transfection of one representative species with the downstream gene. The results obtained thus demonstrate that at least the first five enzymes for heme biosynthesis are absent in all species examined, rendering their transfectants inducible with aminolevulinate to accumulate porphyrins and thus useful as cellular models for human porphyrias.

Original languageEnglish
Pages (from-to)629-636
Number of pages8
JournalExperimental Parasitology
Volume118
Issue number4
DOIs
Publication statusPublished - 2008 Apr 1

Keywords

  • Coproporphyrin
  • Delta-aminolevulinate dehydratase
  • Heme biosynthesis
  • Porphobilinogen deaminase
  • Transgenes
  • Trypanosomatid protozoa
  • Uroporphyrin
  • Uroporphyrinogen decarboxylase

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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