α-1 Antitrypsin binds preprohepcidin intracellularly and prohepcidin in the serum

Edina Pandur, J. Nagy, Viktor S. Poór, Ákos Sarnyai, András Huszár, A. Miseta, Katalin Sipos

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Recent discoveries have indicated that the hormone hepcidin plays a major role in the control of iron homeostasis. Hepcidin regulates the iron level in the blood through the interaction with ferroportin, an iron exporter molecule, causing its internalization and degradation. As a result, hepcidin increases cellular iron sequestration, and decreases the iron concentration in the plasma. Only mature hepcidin (result of the cleavage of prohepcidin by furin proteases) has biological activity; however, prohepcidin, the prohormone form, is also present in the plasma. In this study, we aimed to identify new protein-protein interactions of preprohepcidin, prohepcidin and hepcidin using the BacterioMatch two-hybrid system. Screening assays were carried out on a human liver cDNA library. Preprohepcidin screening gave the following results: α-1 antitrypsin, transthyretin and α-1-acid glycoprotein showed strong interactions with preprohepcidin. We further confirmed and examined the α-1 antitrypsin binding in vitro (glutathione S-transferase, pull down, coimmunoprecipitation, MALDI-TOF) and in vivo (ELISA, cross-linking assay). Our results demonstrated that the serine protease inhibitor α-1 antitrypsin binds preprohepcidin within the cell during maturation. Furthermore, α-1 antitrypsin binds prohepcidin significantly in the plasma. This observation may explain the presence of prohormone in the circulation, as well as the post-translational regulation of the mature hormone level in the blood. In addition, the lack of cleavage protection in patients with α-1 antitrypsin deficiency may be the reason for the disturbance in their iron homeostasis.

Original languageEnglish
Pages (from-to)2012-2021
Number of pages10
JournalFEBS Journal
Volume276
Issue number7
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Hepcidins
Iron
Serum
Plasmas
Assays
Screening
Homeostasis
Blood
Hormones
Furin
Serine Proteinase Inhibitors
Prealbumin
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Bioactivity
Glutathione Transferase
Hybrid systems
Gene Library
Liver
Glycoproteins
Proteins

Keywords

  • α-1 antitrypsin
  • Blood serum
  • Cellular transport
  • Hepcidin
  • Iron transport

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

α-1 Antitrypsin binds preprohepcidin intracellularly and prohepcidin in the serum. / Pandur, Edina; Nagy, J.; Poór, Viktor S.; Sarnyai, Ákos; Huszár, András; Miseta, A.; Sipos, Katalin.

In: FEBS Journal, Vol. 276, No. 7, 04.2009, p. 2012-2021.

Research output: Contribution to journalArticle

Pandur, Edina ; Nagy, J. ; Poór, Viktor S. ; Sarnyai, Ákos ; Huszár, András ; Miseta, A. ; Sipos, Katalin. / α-1 Antitrypsin binds preprohepcidin intracellularly and prohepcidin in the serum. In: FEBS Journal. 2009 ; Vol. 276, No. 7. pp. 2012-2021.
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