Sequence analysis of hepcidin in barbel steed (Hemibarbus labeo): QSHLS motif confers hepcidin iron-regulatory activity but limits its antibacterial activity.

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  • Author(s): Chen J;Chen J; Jiang W; Jiang W; Xu YW; Xu YW; Chen RY; Chen RY; Xu Q; Xu Q
  • Source:
    Developmental and comparative immunology [Dev Comp Immunol] 2021 Jan; Vol. 114, pp. 103845. Date of Electronic Publication: 2020 Sep 01.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: United States NLM ID: 7708205 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0089 (Electronic) Linking ISSN: 0145305X NLM ISO Abbreviation: Dev Comp Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: Tarrytown Ny : Elsevier Science
      Original Publication: Elmsford, N. Y., Pergamon Press., 1977-2004.
    • Subject Terms:
      Aeromonas hydrophila/*physiology ; Amino Acid Motifs/*genetics ; Anti-Bacterial Agents/*metabolism ; Cyprinidae/*immunology ; Fish Proteins/*genetics ; Gram-Negative Bacterial Infections/*immunology ; Hepcidins/*genetics ; Iron/*metabolism ; Liver/*metabolism ; Macrophages/*immunology ; Vibrio Infections/*immunology ; Vibrio vulnificus/*physiology; Animals ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Cells, Cultured ; Cloning, Molecular ; Fish Proteins/metabolism ; Hepcidins/metabolism ; Phylogeny ; Sequence Analysis ; Transcriptome
    • Abstract:
      Fish hepcidin genes are generally classified into two groups: hamp1-and hamp2-type isoforms. Hamp1-type hepcidin exhibits iron regulatory and antimicrobial activity, while hamp2-type shows a unique role in the immune response against various pathogens. An iron-regulatory motif exists at the N-terminus of hamp1-type hepcidin; however, the functional effect of this motif in fish is not well understood. Here, cDNA of the barbel steed (Hemibarbus labeo) hepcidin gene was cloned and sequenced. The predicted amino acid sequence comprised a signal peptide, a prodomain, and a mature peptide. Phylogenetic tree analysis revealed that barbel steed hepcidin belongs to the fish HAMP1 cluster and is closely related to Chinese rare minnow (Gobiocypris rarus) hepcidin. Barbel steed hepcidin is constitutively expressed in healthy fish tissues, predominantly in the liver. Following iron dextran treatment or Aeromonas hydrophila infection, expression of barbel steed hepcidin increased significantly in tested tissues. In vivo administration of intact hepcidin mature peptide (hep25) significantly and dose-dependently reduced ferroportin 1 expression, while truncated hepcidin mature peptide (hep20) lacking a QSHLS motif had no such effect. In vitro treatment of barbel steed monocytes/macrophages with hep25, but not hep20, increased the labile iron pool levels. Hep25 and hep20 conferred antibacterial activity only against A. hydrophila and Vibrio vulnificus, with greater activity of the latter at low concentrations. Neither hep25 nor hep20 impaired the cell membrane integrity of A. hydrophila, but could hydrolyze its genomic DNA; lack of a QSHLS motif enables hep20 to have a better hydrolytic effect. In summary, we identified an iron-regulatory motif in a fish species and demonstrated that this motif confers hamp1-type hepcidin iron-regulatory activity, but attenuates its antibacterial activity.
      (Copyright © 2020 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: Antibacterial activity; Barbel steed; Hepcidin; Iron-regulatory activity; QSHLS motif
    • Accession Number:
      0 (Anti-Bacterial Agents)
      0 (Cation Transport Proteins)
      0 (Fish Proteins)
      0 (Hepcidins)
      0 (metal transporting protein 1)
      E1UOL152H7 (Iron)
    • Publication Date:
      Date Created: 20200905 Date Completed: 20220209 Latest Revision: 20220209
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.dci.2020.103845
    • Accession Number:
      32888968